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  • pharmacokinetics  (76)
  • Zea mays  (50)
  • 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects
  • 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry
  • 04. Solid Earth::04.06. Seismology::04.06.03. Earthquake source and dynamics
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  • Springer  (167)
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  • Springer  (167)
  • AGU
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  • 1995-1999  (167)
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  • 1
    Digitale Medien
    Digitale Medien
    Comparison of the effect of hydroxamic acids from wheat on five species of cereal aphids (1995)
    Springer
    Entomologia experimentalis et applicata 74 (1995), S. 115-119 
    Details
    ISSN: 1570-7458
    Schlagwort(e): wheat ; aphids ; hydroxamic acids ; DIMBOA ; DIMBOA-glucoside ; EPG ; electrical penetration graph ; feeding deterrents ; antixenosis ; plant resistance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Feeding behaviour of five species of cereal aphids in wheat seedlings differing in hydroxamic acid (Hx) levels, was monitored via electrical penetration graphs (EPG). Aphid species could be grouped as sensitive to the feeding deterrent effect of Hx in the seedlings (Rhopalosiphum padi, Schizaphis graminum, Sitobion avenae, andMetopolophium dirhodum) or insensitive to them (Rhopalosiphum maidis). However, when feeding behaviour was studied in artificial diets containing Hx, all species were equally sensitive to Hx. The behavour ofR. maidis was further compared with that ofR. padi through detailed EPG analysis. It was found that the insensitivity ofR. maidis to Hx in seedlings may be due to a feeding strategy avoiding contact with the compounds by decreasing the number of cellular punctures in live tissues other than sieve elements during its way to the phloem.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02383002
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  • 2
    Digitale Medien
    Digitale Medien
    Hypersensitive response of wheat to the Hessian fly (1995)
    Springer
    Entomologia experimentalis et applicata 74 (1995), S. 283-294 
    Details
    ISSN: 1570-7458
    Schlagwort(e): hypersensitivity ; Hessian fly ; plant resistance ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Hessian flyMayetiola destructor (Say) larvae are able to obtain food from their host plant without inflicting mechanical damage to the plant surface, apparently by secreting substances which elicit release of nutrients from plant cells surrounding the feeding site. Cells of fully susceptible plants retain their normal appearances, while in resistant plants extensive areas of cellular collapse occur. These responses indicate that hypersensitivity is the basis of wheat's resistance to the Hessian fly. The fly's feeding mechanism more closely resembles that of a pathogen than of a phytophagous insect; correspondingly, both the genetic relationship and resistance mechanism of the host plant to the parasite are of the sorts commonly associated with bacterial and fungal pathogens.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02381793
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  • 3
    Digitale Medien
    Digitale Medien
    Inheritance of resistance in maize silks to the corn earworm (1995)
    Springer
    Entomologia experimentalis et applicata 77 (1995), S. 315-321 
    Details
    ISSN: 1570-7458
    Schlagwort(e): Insecta ; Helicoverpa zea ; Zea mays ; resistance inheritance ; joint scaling test ; additive-dominance model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The corn earworm,Helicoverpa zea (Boddie), is a perennial economic pest of field crops in the United States. Maize,Zea mays L., is the major host crop promoting the build-up of devastating corn earworm populations that limit full production of cotton, soybean, peanut, and grain sorghum. Resistance to the corn earworm in maize and in particular sweet maize, would provide an environmentally safe, economical method of control for this pest insect. Antibiotic effects of corn silks on this insect are: small larvae, extended developmental period, and reduced fecundity. Silks from individual maize plants of resistant and susceptible lines and progeny in six generations consisting of parents (P1, P2), F1, F2, and backcrosses BC1.1 (F1 × P1) and BC1.2 (F1 × P2) from each of four crosses were used to determine the genetic basis of the antibiotic resistance of silks to the corn earworm. In the cross of Zapalote Chico × PI340856, genes controlling resistance in the silks to the corn earworm larvae are dominant in PI340856 to those in Zapalote Chico. The cross of Zapalote Chico × GT114 involves parents differing in degree of resistance, and possibly differing for the genetic mechanism by which the resistance is inherited. The inheritance of resistance may involve non-additive (dominance and epistasis) genetic variance. A digenic 6-parameter model indicated (1) the resistance in this cross is controlled by more than one pair of genes and (2) some or all of the genes interact to cause non-allelic interaction. Thus, the resistance in this cross may be controlled by both dominant and recessive genes. The resistance of Zapalote Chico × CI64, an intermediate inbred, is influenced by additive gene effects. The digenic model adequately predicts all generation means of the cross of GT3 × PI340856 except for the F1. Thus, it appears that the additive-dominance model is not satisfactory for this cross involving susceptible and resistant parents. Generation mean analysis indicates that resistance to silk-feeding by corn earworm larvae is under genetic control, but gene action differs from one type of cross to another.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02383066
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  • 4
    Digitale Medien
    Digitale Medien
    Effects of a vesicular-arbuscular mycorrhizal fungus and other soil microorganisms on growth, mineral nutrient acquisition and root exudation of soil-grown maize plants (1995)
    Springer
    Mycorrhiza 5 (1995), S. 321-327 
    Details
    ISSN: 1432-1890
    Schlagwort(e): Glomus mosseae ; Zea mays ; Mineral uptake ; Root exudation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Maize (Zea mays L. cv. Alize) plants were grown in a calcareous soil in pots divided by 30-μm nylon nets into three compartments, the central one for root growth and the outer ones for hyphal growth. Sterle soil was inoculated with either (1) rhizosphere microorganisms other than vesicular-arbuscular mycorrhizal (VAM) fungi, (2) rhizosphere microorganisms together with a VAM fungus [Glomus mosseae (Nicol. and Gerd.) Gerdemann and Trappel], or (3) with a gamma-irradiated inoculum as control. Plants were grown under controlled-climate conditions and harvested after 3 or 6 weeks. VAM plants had higher shoot∶root ratios than non-VAM plants. After 6 weeks, the concentrations of P, Zn and Cu in roots and shoots had significantly increased with VAM colonization, whereas Mn concentrations had significantly decreased. Root exudates were collected on agar sheets placed on the interface between root and hyphal compartments. Six-week-old VAM and non-VAM plants had similar root exudate compositions of 72–73% reducing sugars, 17–18% phenolics, 7% organic acids and 3% amino acids. In another experiment in which root exudates were collected on agar sheets with or without antibiotics, the amounts of amino acids and carbohydrates recovered were similar in VAM and non-VAM plants. However, threeto sixfold higher amounts of carbohydrates, amino acids and phenolics were recovered when antibiotics were added to the agar sheets. Thus, the high microbial activity in the rhizosphere and on the rhizoplane limits the exudates recovered from roots.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00207404
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  • 5
    Digitale Medien
    Digitale Medien
    Effects of a vesicular-arbuscular mycorrhizal fungus and other soil microorganisms on growth, mineral nutrient acquisition and root exudation of soil-grown maize plants (1995)
    Springer
    Mycorrhiza 5 (1995), S. 321-327 
    Details
    ISSN: 1432-1890
    Schlagwort(e): Key words Glomus mosseae ; Zea mays ; Mineral uptake ; Root exudation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract  Maize (Zea mays L. cv. Alize) plants were grown in a calcareous soil in pots divided by 30-μm nylon nets into three compartments, the central one for root growth and the outer ones for hyphal growth. Sterile soil was inoculated with either (1) rhizosphere microorganisms other than vesicular-arbuscular mycorrhizal (VAM) fungi, (2) rhizosphere microorganisms together with a VAM fungus [Glomus mosseae (Nicol. and Gerd.) Gerdemann and Trappel], or (3) with a gamma-irradiated inoculum as control. Plants were grown under controlled-climate conditions and harvested after 3 or 6 weeks. VAM plants had higher shoot : root ratios than non-VAM plants. After 6 weeks, the concentrations of P, Zn and Cu in roots and shoots had significantly increased with VAM colonization, whereas Mn concentrations had significantly decreased. Root exudates were collected on agar sheets placed on the interface between root and hyphal compartments. Six-week-old VAM and non-VAM plants had similar root exudate compositions of 72–73% reducing sugars, 17–18% phenolics, 7% organic acids and 3% amino acids. In another experiment in which root exudates were collected on agar sheets with or without antibiotics, the amounts of amino acids and carbohydrates recovered were similar in VAM and non-VAM plants. However, three- to sixfold higher amounts of carbohydrates, amino acids and phenolics were recovered when antibiotics were added to the agar sheets. Thus, the high microbial activity in the rhizosphere and on the rhizoplane limits the exudates recovered from roots.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s005720050079
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  • 6
    Digitale Medien
    Digitale Medien
    Bioavailability of heavy metals and abundance of arbuscular mycorrhiza in a soil polluted by atmospheric deposition from a smelter (1995)
    Springer
    Biology and fertility of soils 19 (1995), S. 22-28 
    Details
    ISSN: 1432-0789
    Schlagwort(e): Arbuscular mycorrhiza ; Limed silty loam Heavy metals ; Pb-Zn smelter ; Root colonization Spore numbers ; Tolerance ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Geologie und Paläontologie , Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract The bioavailability of heavy metals (Cd, Zn, Pb, Cu) and the abundance of arbuscular mycorrhiza (AM) were studied in two agricultural fields close to a Pb-Zn smelter and three fields outside the pollution zone all cultivated with maize (Zea mays L.). Metal extractability with ethylenediaminetetraacetic acid (EDTA)-NH4OAc and Ca(NO3)2, plant metal uptake, and mycorrhizal parameters (spore number, root colonization) were assessed at two growth stages (six-leaf and maturity). Despite regular liming, the availability of Cd, Zn, and Pb was markedly higher in the two metal-polluted fields than in the three uncontaminated fields. However, the AM abundance was not correlated with metal availability. Root colonization and spore numbers in the metal polluted fields were relatively high, though at plant maturity the former was significantly lower than in one of the uncontaminated fields. The very low AM abundance in the two other unpolluted fields was related to other factors, particular soil and plant P status and soil pH. AM root colonization did not substantially prevent plant metal accumulation, since the metal concentrations in maize grown on the polluted fields strongly exceeded normal values, and for Cd and Pb reached the limits of toxicity for animal feed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00336342
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  • 7
    Digitale Medien
    Digitale Medien
    Nitrogen use in maize-grain legume cropping systems in semi-arid Kenya (1995)
    Springer
    Biology and fertility of soils 20 (1995), S. 57-62 
    Details
    ISSN: 1432-0789
    Schlagwort(e): Nitrogen use ; Nitrogen fertilizer recovery ; Zea mays ; Phaseolus vulgaris ; Vigna unguiculata ; Nitrogen fixation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Geologie und Paläontologie , Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Locally suitable cultivars of maize, beans, and cowpeas were grown in field experiments for four seasons in semi-arid Kenya. For three seasons, the dry matter production and grain yield of maize and beans were not increased by N fertilizer additions up to 120 kg N ha-1. Fertilizer recoveries measured by 15N isotope dilution techniques were low, less than 20%. Inoculated and uninoculated beans failed to fix N2. By contrast the cowpea derived 50% of its N from fixation, equivalent to 197 kg N ha-1. The N content of the grain generally exceeded 40 kg N ha-1, and the N content of the seeds from the grain legumes were greater than those from the cereals. Large inputs of N fertilizer or N by fixation are required if maize-grain legume cropping system in semiarid Kenya are to be sustained in the long term.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00307842
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  • 8
    Digitale Medien
    Digitale Medien
    Enterobacter cloacae is an endophytic symbiont of corn (1995)
    Springer
    Mycopathologia 129 (1995), S. 117-125 
    Details
    ISSN: 1573-0832
    Schlagwort(e): Biological control ; Corn seedling disease ; Enterobacter cloacae ; Fusarium moniliforme ; Maize ; Seedling blight ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The bacteriumEnterobacter cloacae is presently used for biocontrol of postharvest diseases of fruits and vegetables and as a preplant seed treatment for suppression of damping-off. This bacterium has apparent affinities for several grass species, but it is not considered to be an endophyte. While screening corn for fungi and bacteria with potential for biocontrol of various corn diseases, the surface-sterilized kernels of one unknown Italian corn cultivar produced fungus-free corn seedlings with roots endophytically infected byE. cloacae. This paper describes the microscopic nature ofE. cloacae RRC 101 with corn, and the in vitro control ofFusarium moniliforme and other fungi with this bacterium. Light and electron microscopy determined that this isolate ofE. cloacae was biologically associated with corn seedling roots, where it was distributed intercellularly within the cortex and stele. This is a first report of a strain of this bacterium as an endophytic symbiont of roots. Following a topical application ofE. cloacae to kernels, and upon germination this bacterium readily infected roots of two other corn cultivars. The bacterium was observed within the endosperm of germinating corn seedling, but germination was not affected. Further, the bacterium was isolated from leaves and stems of 3- to 6-week-old seedlings indicating that the above ground portions of corn were also colonized. There was no evidence of damage to cells of the root during a three to four week observation period. This bacterium was antagonistic to several isolates of the corn pathogenFusarium moniliforme, and to two other species of fungi, all of which produce mycotoxins on corn.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01103471
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  • 9
    Digitale Medien
    Digitale Medien
    The phytotoxicity of selected mycotoxins on mature, germinatingZea mays embryos (1995)
    Springer
    Mycopathologia 132 (1995), S. 173-183 
    Details
    ISSN: 1573-0832
    Schlagwort(e): Deoxynivalenol ; Embryo ; Mature ; Ochratoxin ; Plantlet ; Zearalenone ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Mature maize (Zea mays) embryos were exposed to 5, 10 and 25 µg ml−1 of deoxynivalenol (DON), zearalenone (ZEA), ochratoxin A (OA) and a mixture of zearalenone and deoxynivalenol (ZEA/DON) for 9 days. DON and the ZEA/DON combination were consistently more inhibitory of the measured parameters than either ZEA or OA. Based on the predicted additive values, it would appear that, in combination, ZEA and DON act synergistically to inhibit root and shoot growth. For ZEA alone, a concentration of 5 µg ml−1 ZEA was generally inhibitory of root and shoot elongation and fresh mass accumulation, while at 10 and 25 µg ml−1, this toxin had a stimulatory effect on these parameters. For OA, the measured effects on root and shoot growth at 5 and 25 µg ml−1 were stimulatory, while at 10 µg ml−1 OA, an inhibitory effect was observed. For all toxins, inhibitory/stimulatory effects were generally more marked for root parameters than for shoot elongation or mass.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01103984
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  • 10
    Digitale Medien
    Digitale Medien
    Estimation of the contribution of biological N2 fixation to twoPhaseolus vulgaris genotypes using simulation of plant nitrogen uptake from15N-labelled soil (1995)
    Springer
    Nutrient cycling in agroecosystems 45 (1995), S. 169-185 
    Details
    ISSN: 1573-0867
    Schlagwort(e): 15N ; non-nod beans ; quantification of N2 fixation ; reference crops ; simulation technique ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract A technique for the application of the15N isotope dilution technique for the quantification of plant associated biological nitrogen fixation (BNF) was tested and applied to quantify the BNF contribution to two genotypes ofPhaseolus vulgaris. The technique makes use of sequential measurements of the15N enrichment of soil mineral N, and the uptake of labelled N by the “N2-fixing” plant, to simulate its uptake of soil N (the “soil to plant simulation” technique). The test was made with two non-N2-fixing crops (non-nodulating beans and wheat) and two bean genotypes (PR 923450 and Puebla 152), at two levels of N fertilizer addition (10 and 40 kg N ha−1), to compare the actual N uptake with that simulated from the soil and crop15N data. The simulation of the soil N uptake by the non-nod bean crop using this “soil to plant simulation” technique underestimated by 20 to 30% the true N uptake, suggesting that the mineral N extracted from soil samples taken from the 0–15cm layer had a higher15N enrichment than that N sampled by the roots of this crop. In the case of the wheat crop the simulation resulted in a much greater underestimation of actual N uptake. In general the results using this technique suggested that BNF inputs to the bean cultivars was higher than would be expected from the nodulation and acetylene reduction data, except for the early PR beans in the 40 kg N ha−1 treatment. In this case the total N and simulated soil N accumulation were well matched suggesting no BNF inputs. An allied technique (the “plant to plant simulation technique”) was proposed where the15N enrichrnent of soil mineral N was simulated from the data for total N and labelled N accumulation taken from sequential harvests of either of the non-N2 -fixing control crops. This was then utilized in combination with the labelled N uptake data of the other crop to simulate its soil N uptake. However, the results using either technique indicated that the wheat and non-nod or nodulating beans exploited pools of N in the soil with completely different15N enrichments probably due to differences in exploitation of the soil N with depth.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00748587
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  • 11
    Digitale Medien
    Digitale Medien
    Effect of climate on the recovery in crop and soil of15N-labelled fertilizer applied to wheat (1995)
    Springer
    Nutrient cycling in agroecosystems 45 (1995), S. 209-215 
    Details
    ISSN: 1573-0867
    Schlagwort(e): climate ; fertilizer recovery ; 15N fertilizer ; precipitation-evaporation quotient ; soil ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Data was assembled from experiments on the fate of15N-labelled fertilizer applied to wheat (Triticum spp.) grown in different parts of the world. These data were then ranked according to the annual precipitation-evaporation quotient for each experimental location calculated from the average long-term values of precipitation and potential evaporation. Percentage recovery of15N fertilizer in crop and soil varied with location in accordance with the precipitation-evaporation quotient. In humid environments more15N fertilizer was recovered in the crop than in the soil, while in dry environments more15N fertilizer was recovered in the soil than in the crop. Irrespective of climatic differences between locations 20% (on average) of the15N fertilizer applied to wheat crops was unaccounted for at harvest. Most of the15N fertilizer remaining in the soil was found in the 0–30 cm layer. The most likely explanation of these differences is that wheat grown in dry environments has a greater root:shoot ratio than wheat grown in humid environments and, further, that the residue of dryland crops have higher C/N ratios. Both factors could contribute to the greater recovery of15N fertilizer in the soil in dry environments than in humid ones.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00748591
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  • 12
    Digitale Medien
    Digitale Medien
    Nitrogen, phosphorus and potassium relations in five major cereals reviewed in respect to fertilizer recommendations using simulation modelling (1995)
    Springer
    Nutrient cycling in agroecosystems 44 (1995), S. 37-49 
    Details
    ISSN: 1573-0867
    Schlagwort(e): millet ; sorghum ; rice ; maize ; wheat ; nutrient harvest index ; post-anthesis nutrient uptake ; recovery fraction ; simulation modelling
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract In land use plans, fertilizer recommendations are indispensable to avoid soil nutrient depletion or soil water pollution. Nutrient relations of five cereals have been evaluated on the basis of a literature review with the aim of arriving at such fertilizer recommendations at regional level. Nutrients considered were nitrogen, phosphorus and potassium for millet, sorghum, maize, rice and wheat. The relevant nutrient relations are fertilizer nutrient application to nutrient uptake, and nutrient uptake to crop yield. In addition, post-anthesis nutrient uptake is considered. Subsequently, obtained results are used in simulation modelling exercises to calculate the time required to attain an equilibrium nutrient balance and to investigate the effect of erosion control and straw recycling. Although fertilizer requirements could be assessed for each of the five cereals, monitoring of nutrient supply from natural sources remains necessary. Moreover, research on fertilizer use should focus on improvement of fertilizer recoveries and multiperiod models for both N and P uptakes by crops to allow quantitative land use planning where the time scale is included.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00750691
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  • 13
    Digitale Medien
    Digitale Medien
    The effect of foliar supplements of potassium nitrate and urea on the yield of winter wheat (1995)
    Springer
    Nutrient cycling in agroecosystems 44 (1995), S. 217-223 
    Details
    ISSN: 1573-0867
    Schlagwort(e): foliar fertilizer ; nitrate ; potassium ; urea ; wheat ; yield
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Winter wheat crops were grown with ostensibly adequate supplies of all soil nutrients in 1990 and 1991 with the aim of testing if late foliar supplements of K and N, applied at key development stages, could improve grain yield and grain N content. Foliar sprays of KNO3 solution, supplying up to 40 kg K ha−1 in total, at flag leaf unfolded, inflorescence completed and the watery-ripe stage of grain filling, had no effect on yield, yield components or grain N. Urea, supplying 40 kg N ha−1 at flag leaf unfolded, had no effects on grain yield and grain N in 1990, but in 1991 grain N was increased by 0.14% whilst yield was reduced by up to 0.6 t ha−1. Urea scorched flag leaf tips in both years. In 1990, the spring was very dry and foliar supplements might have been expected to have had an effect, but on this highly fertile soil all crop K and N requirements were met from the soil.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00750928
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  • 14
    Digitale Medien
    Digitale Medien
    Selenium concentration in spring wheat as influenced by basal application and top dressing of selenium-enriched fertilizers (1995)
    Springer
    Nutrient cycling in agroecosystems 45 (1995), S. 163-167 
    Details
    ISSN: 1573-0867
    Schlagwort(e): Basal dressing ; Se-enriched fertilizers ; Se-uptake ; soil texture ; top-dressing ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract A multisite field experiment was conducted to study the effect of topdressed Se-enriched Ca(NO3)2 (CN) and basal applied NPK on the selenium (Se) concentration in spring wheat (Triticum aestivum L.). Selenium was applied either through CN (at the rates of 0, 6.45, and 12.91 g Se ha−1) or NPK (5.83 g Se ha−1). Selenium concentration in wheat grains increased consistently with increasing rate of Se-enriched CN or NPK. However, the superiority of Se-enriched CN over NPK in raising the Se concentration in wheat grain depended on location and growth conditions. At the same rate both methods of Se-application were found to be equally effective in raising the Se concentration of wheat grains. The Se concentration of grain was generally higher in the light textured soils than in the medium to heavy textured soils. Without Se application, the Se-concentration in wheat grain was about 16µg kg−1 which is regarded insufficient to meet the Se requirement for Se in animal and human. Calcium nitrate enriched with 25 mg Se kg−1 (6.45 g Se ha−1) increased the Se concentration in wheat grain to a desired level.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00790666
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  • 15
    Digitale Medien
    Digitale Medien
    Deleterious effect of minimal enzymatic treatments on the development of isolated maize embryo sacs in culture (1995)
    Springer
    Sexual plant reproduction 8 (1995), S. 313-317 
    Details
    ISSN: 1432-2145
    Schlagwort(e): Embryo sac ; Zea mays ; Enzymatic isolation ; Zygotic embryogenesis ; Microinjection
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The long-term viability of isolated embryo sacs was studied in maize. Fertilised embryo sacs were digested in order to remove most of the nucellus cells present on their surfaces and then transferred to culture. Experiments on 161 embryo sacs showed that isolation treatments using even minimal enzymatic digestion affected the further development of the embryo sacs. Few embryo sacs survived in culture and those produced only abnormal embryos; they produced no plants. We concluded that embryo sacs isolated through enzymatic digestion may offer limited prospects for long-term studies where normal embryogenic development is required. Alternative strategies are discussed for maize.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00229389
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  • 16
    Digitale Medien
    Digitale Medien
    Effects of calcium, magnesium, potassium and boron on sperm cells isolated from pollen of Zea mays L. (1995)
    Springer
    Sexual plant reproduction 8 (1995), S. 113-122 
    Details
    ISSN: 1432-2145
    Schlagwort(e): Zea mays ; Calcium ; Cell integrity ; Cell viability ; Sperm cell
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Our previous studies showed that Brewbaker and Kwack salts, which have been widely used in pollen germination and sperm isolation, are not appropriate for the maintenance of isolated maize (Zea mays L.) sperm cells. In the present study, we have characterized the effects of each BKS component salt on the integrity of isolated sperm cells using hemacytometry. At 0.01 and 0.1 mM, there were no differences in cell number between control and any salt-treated cells except a 22% decrease with 0.1 mM MgSO4 at 48 h. At the 1 mM level, cell number decreased with time in the presence of Ca(NO3)2 and MgSO4, with loss of integrity of most cells at 48 h, while KNO3 and H3BO3 had little or no effect. Further characterization of calcium-induced reduction in cell integrity using flow cytometry showed that depletion of possible residual free calcium by addition of EGTA to the suspension medium improved cell longevity and viability. Exposure of isolated sperm cells to 1 mM calcium had no effect on cell integrity and viability in 5 h; however, only 12% of cells remained intact at 24 h. The reduction in cell integrity was hastened when cells were pretreated with the calcium ionophore A23187 prior to exposure to 1 mM calcium, with a 54% reduction in cell number at 1 h and complete cell lysis at 24 h. However, depletion of cytosolic free calcium by pretreatment of cells with the calcium ionophore followed by resuspension in the presence of EGTA resulted in rapid reduction of cell integrity as well. These results collectively suggest that maize sperm cells are sensitive to exogenous free calcium; however, a certain level of cytosolic free calcium is necessary for maintenance of integrity. Mechanisms of calcium-induced reduction in cell integrity are discussed along with possible roles of the sensitivity of sperm cells to calcium in fertilization.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00230898
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  • 17
    Digitale Medien
    Digitale Medien
    Methotrexate in juvenile rheumatoid arthritis (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 507-511 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Methotrexate ; Juvenile rheumatoid arthritis ; pharmacokinetics ; age dependence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Children with juvenile rheumatoid arthritis (JRA) have been reported to require higher doses (per kg body weight) of methotrexate (MTX) than adults with rheumatoid arthritis to control their disease. The purpose of the present study was to characterise the plasma pharmacokinetics of MTX and its major metabolite, 7-hydroxymethotrexate (7-OHMTX) in children, and to compare the results with those previously obtained in adults. Thirteen patients (age 5–16 y) with JRA (median disease duration 5.5 y) were studied after once weekly oral administration of MTX (median 0.21 mg·kg−1). The analytical method was sufficiently sensitive to permit determination of plasma and urinary concentrations of MTX and 7-OHMTX during the entire dose interval in most of the patients. The dose normalized area under the plasma concentration versus time-curve (AUC) of MTX increased with the age of the children and was lower than previously found in adults. The dose normalized AUC of 7-OHMTX was not dependent on age. No correlation was found between the AUCs of MTX and 7-OHMTX. The results suggest that the age-dependence of the pharmacokinetics of MTX might explain the observation that at least some children require higher doses of MTX than adults to obtain a sufficient therapeutic effect.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00193703
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  • 18
    Digitale Medien
    Digitale Medien
    Antipyrine disposition in obesity: evidence for negligible effect of obesity on hepatic oxidative metabolism (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 525-530 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Antipyrine disposition ; Obesity ; pharmacokinetics ; oxidative metabolism ; weight reduction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Following an overnight fast and 2 days of abstention from caffeine, a single 1.0-g oral dose of antipyrine was administered to 20 obese but otherwise healthy subjects (group A) and 11 healthy volunteers (group B). Weight, Body Mass Index (BMI) and % of Ideal Body Weight (IBW) were significantly greater in the obese than in the lean group. (Mean 110.4 vs 62.7 kg; 38.5 vs 22.3 kg · m−2 and 181vs 106 % respectively). In a subgroup of 6 obese subjects (group C) antipyrine was given again 11.3 months later after a 29.8 kg mean weight loss. Antipyrine apparent volume of distribution (V) and elimination half-life (t 1/2) were significantly greater in the obese than in the lean group (V 49.9 vs 34.3 l respectively; t 1/2 15.5 vs 12.0 h respectively), but its clearance rate (CLo) values were similar. V corrected for total body weight was significantly reduced in group A than in group B (0.45 vs 0.55 l · kg−1 respectively). Stratified comparison of antipyrine pharmacokinetics between obese and lean subjects according to age, gender and smoking habits did not alter the overall results. In group C, weight reduction was associated with a significant decrease in antipyrine V (from 51.8 to 47.5 l) and t 1/2 (from 15.1 to 12.7 h), and a non-significant increase in antipyrine CLo. We conclude that in severely obese subjects, antipyrine total V is mildly increased but V corrected for total body weight is significantly decreased. In addition, obesity is associated with a slight prolongation of antipyrine t 1/2 whereas its CLo is unaltered. These findings may indicate that obesity, even in its extreme form, has a negligible effect on the oxidative metabolic capacity of the liver.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00193706
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  • 19
    Digitale Medien
    Digitale Medien
    Oral bioavailability of CHF1194, an inclusion complex of piroxicam and β-cyclodextrin, in healthy subjects under single dose and steady-state conditions (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 531-536 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Piroxicam ; β-Cyclodextrin ; pharmacokinetics ; healthy volunteers ; multiple dose ; adverse event
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract CHF1194 is an inclusion complex of β-cyclodextrin with the nonsteroidal anti-inflammatory drug piroxicam. In man, β-cyclodextrin acts as a carrier of piroxicam. As the inclusion complex of piroxicam-β-cyclodextrin is wettable and more water soluble, the absorption rate of the drug is increased whilst its other pharmacokinetic characteristics remain unchanged. The aim of the present study in 12 healthy subjects was to compare the oral bioavailability of 20 mg piroxicam in a CHF1194 tablet and a plain piroxicam capsule after a single dose and after two weeks of once daily administration, and also to assess the plasma levels and urinary excretion of β-cyclodextrin after CHF1194 administration. The two treatments were administered in cross-over fashion, separated by a wash-out period of three weeks. Piroxicam, 5′-hydroxypiroxicam and β-cyclodextrin were monitored in plasma and urine for 120 h after the first and last doses. Clinical tolerance was excellent and no adverse event occurred during either phase of the study. The extent of absorption of piroxicam from the CHF1194 tablet after the single dose was equivalent to that after the plain piroxicam capsule, within confidence limits of less than 80–125%. After repeated dosing, CHF1194 yielded the same steady-state systemic concentrations of piroxicam and 5′-hydroxypiroxicam as the reference capsule, and similar excretion pattern of the metabolite. After both single and multiple dosing, piroxicam was absorbed more rapidly after CHF1194, an expected consequence of the complexation of piroxicam with β-cyclodextrin. This may be of therapeutic interest as it might accelerate the onset of pain relief. The pharmacokinetics of piroxicam was linear after the doses used here, suggesting that long term treatment with CHF1194 should not require any change in dosing regimen. Even after 14 days of repeated administration of CHF1194, β-cyclodextrin could not be detected in plasma or urine, suggesting that in man the unchanged oligosaccharide was absorbed to a very small extent.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00193707
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  • 20
    Digitale Medien
    Digitale Medien
    Furosemide disposition in patients on CAPD (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 385-390 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Furosemide ; Dialysis ; continuous ambulatory peritoneal ; drug disposition ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Single doses of oral and intravenous furosemide were given to 8 healthy male volunteers (40 mg) and 11 patients with renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD) (80 mg). In the volunteers, absorption was variable. Only one half of the intravenous dose and one third of the oral dose was available for renal pharmacological action as judged by the urinary recovery. In the patients, absorption was also variable and was markedly delayed (t max 128 vs 90 min) but more complete (bioavailability 70.1 vs 53.6%). The differences between the two groups were not significant, however (95% C.I.: -90 to 30 and -40.4 to 7.5 respectively). The mean elimination half-life was significantly longer in the patients following both the oral (228 vs 65.1 min) and intravenous dose (195 vs 60.3 min). The total body clearance of furosemide in the volunteers was 138 ml·min−1 and this was much lower in the CAPD patients (61.9 ml·min−1) in whom the renal clearance was minimal. The peritoneal clearance of furosemide was negligible. Although there were trends indicating differences in absorption between the two groups, the significant differences in furosemide disposition observed in CAPD patients were due to renal failure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00194955
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  • 21
    Digitale Medien
    Digitale Medien
    Effects of altitude (4300 M) on the pharmacokinetics of caffeine and cardio-green in humans (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 167-170 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Caffeine ; Cardio-green ; Indocyanine Green ; altitude ; metabolism ; pharmacokinetics ; hypoxia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The effects of chronic exposure to high altitude on the pharmacokinetics of caffeine and cardiogreen (ICG) were examined in eight healthy males (23–35 y) at sea level (SEA) and following 16 days residence at 4300 m (ALT). ICG (0.5 mg · kg−1) was administered as an intravenous bolus and caffeine (4 mg · kg−1) in an orally ingested solution. The concentration of ICG, caffeine, and the primary metabolites of caffeine (MET) were determined in serial blood samples and their pharmacokinetics computed. In comparison to SEA, ALT resulted in a significant decrease in the caffeine half-life (t1/2, 4.7 vs 6.7 h) and area under the curve (2.5 vs 3.7 g · 1−1 · min−1), and increased clearance (117 vs 86 ml · min−1 · 70 kg−1). In ALT the area under the curve of ICG significantly decreased (85 vs 207 mg · 1−1 · min−1) and the volume of distribution and clearance increased (5.2 vs 2.41 and 532 vs 234 ml · min−1 respectively) compared to SEA. There was a significant increase in the AUC ratio of MET to caffeine indicating that either metabolite formation or elimination was increased in ALT. These results demonstrate that in humans, chronic exposure to 4300 m results in the modification of the pharmacokinetics of caffeine and ICG.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00192744
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  • 22
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and bioavailability of a sustained-release diltiazem formulation (Mono-Tildiem LP 300 mg) after repeated administration in healthy volunteers (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 259-264 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Diltiazem ; sustained-release formulation ; pharmacokinetics ; bioavailability ; bioequivalence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The usual dosage regimen of diltiazem (Tildiem) is 60 mg 3–4 times a day. A sustained-release formulation has been developed (Mono-Tildiem LP 300 mg) in order to allow a single daily administration. Two repeated dosing studies were performed in healthy volunteers. The absolute bioavailability of sustained-release diltiazem LP 300 mg was investigated using concomitant i.v. administration of 13C-labelled drug: absolute bioavailability of the “once a day” formulation was 35%. The second study compared sustained-release diltiazem LP 300 mg with the standard formulation of diltiazem. The results showed that the diltiazem plasma concentrations obtained after the LP formulation remained stable between 2 and 14 h after administration and were compatible with a once a day administration. Relative bioavailability of sustained-release diltiazem LP 300 mg was 79.3% compared with diltiazem. Therefore, a unitary dose of sustained-release diltiazem LP 300 mg was chosen as the dose equivalent to the daily dose administered with the standard diltiazem formulation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00198308
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  • 23
    Digitale Medien
    Digitale Medien
    Disposition of lorazepam in diabetes: differences between patients treated with beef/pork and human insulins (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 253-258 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Diabetes ; Human insulin ; Lorazepam ; pharmacokinetics ; glucuronidation ; enterohepatic circulation ; animal insulin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The pharmacokinetics of lorazepam was examined in 10 male patients with insulin-dependent diabetes mellitus before and following treatment with neomycin and cholestyramine. Neomycin and cholestyramine were given in an attempt to block the enterohepatic circulation of lorazepam and so to permit an in vivo estimate of hepatic glucuronidation. The volume of distribution and clearance of free lorazepam in diabetic patients were not significantly different from the corresponding estimates in 14 normal controls. Neomycin and cholestyramine increased the clearance of lorazepam by 63% consistent with their effect in non-diabetic controls. However, patients on beef/pork insulin exhibited a greater than normal increase on this interupting regimen (125%), and had a significantly greater neomycin/cholestyramine cycling-interrupted clearance of lorazepam than either normal controls or patients on human insulin (15.4 vs. 6.96 and 7.87 ml·min−1·kg−1). The clearance was correlated positively and significantly with HbA1c and glycated proteins (fructosamine), but only in patients on human insulin. Thus, the pharmacokinetics of lorazepam was not altered in patients with insulin-dependent diabetes mellitus. However, it is possible that there are differences in the rate and extent of hepatic glucuronidation and enterohepatic circulation of lorazepam between patients treated with beef/pork and human insulins and between diabetics treated with beef/pork insulin and non-diabetic controls.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00198307
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  • 24
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of 5-aminosalicylic acid from controlled-release capsules in man (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 273-277 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Mesalamine ; 5-aminosalicylic acid ; controlled release capsules ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract One gram single dose of Pentasa controlled-release capsules was administered to 24 healthy volunteers under fasting condition. Mean plasma 5-aminosalicylic acid (5-ASA) and acetyl 5-ASA concentrations peaked at 0.53 μg · ml−1 and 1.33 μg · ml−1 from 3 to 4 hours following dosing, respectively. The half-lives of both compounds could not be determined as absorption of 5-ASA was continuous throughout the gastrointestinal tract. An average of 29.4% (CV: 27%) of the dose was excreted in the urine primarily as acetyl 5-ASA. Up to 91.1% of the dose was released from the capsules. Forty percent of the dose (CV: 40%) was eliminated in the feces, with 8.9% of the dose remained as formulation bounded 5-ASA, indicating that controlled-release capsules continue to release drug throughout the GI tract. 5-ASA contributed 46.7% of the salicylates eliminated in the feces and acetyl 5-ASA accounted for the balance. Controlled-release capsules produced three times more total salicylates and 10 times more total and free 5-ASA in the feces than did 5-ASA suspension. Thus, while lower systemic levels of salicylates were absorbed, greater therapeutic quantities of 5-ASA were available in the bowel.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00198311
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  • 25
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of thiopental after single and multiple intravenous doses in critical care patients (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 127-137 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Thiopental ; Pharmacokinetic modelling ; pharmacokinetics ; single dose ; multiple dosing ; neurosurgical patients ; variability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Thiopental was administered to neurosurgical patients for cerebral protection and its pharmacokinetic parameters were determined after a single bolus of 540, 1000 or 1500 mg (3 subjects) or after multiple doses of 250 mg (5 subjects) and 500 mg (2 subjects) every two hours for up to 7 days. The data were analysed by a two- or three- compartment model and linear kinetics. After a single IV bolus, the mean initial volume of distribution (V1) was 0.4811·kg−1, and the steady-state volume of distribution (Vss) was 2.16 1·kg−1. The distribution (t1/2α) and elimination (t1/2β) half-lives were 0.590 and 5.89 h, respectively, and the mean residence time (MRT) was 7.44 h. The clearance was 5.41 ml·min−1·kg−1. With repeated injections, the pharmacokinetic parameters for each patient were estimated taking into account all administered doses and blood samples, which were taken whenever possible daily at steady state and after the last dose. The variability observed in the pharmacokinetic parameters of thiopental reflected by the coefficient of variation (CV%) was wide but was of similar magnitude within patients (CVintra) as it was between patients (CVinter). The steady-state trough plasma concentration (Cmin obs) ranged from 4.8 to 30 mg·1−1 (mean 16.0 mg·1−1 and median 14.3 mg·1−1). Peak concentrations (Cmax obs) ranged from 8.35 to 45 mg·1−1 (25.4 mg·1−1, and median 23.3 mg·1−1). The values of V1 and Vss were similar to those obtained after a single dose. For V1, the mean was 0.333 1·kg−1. The mean Vss was 2.68 1·kg−1, with a CVintra of 12.6 to 56% and a CVinter of 13.2%. A shorter distribution half-life t1/2α was noted on multiple dosing; the mean value was 0.122 h. The elimination half-life t1/2β and the mean residence time became longer due to a decrease in clearance. For t1/2β the mean value was 16.3 h. The mean MRT was 21.9 h, CVintra 9.19 to 48.5%, and the CVinter 35.3%. The mean clearance was 2.16 ml·min−1·kg−1, CVintra 7.28 to 25.5%, and the CVinter 20.4%. This value is 50% lower than after a single dose. Identification of the kinetic parameters of thiopental allows simulation of the effects of doses on subsequent plasma levels and will permit a priori prediction of day to day adjustment of drug dosage.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00192371
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  • 26
    Digitale Medien
    Digitale Medien
    Limitations of the maximum entropy principle in devising drug input rate (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 139-143 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Intestinal absorption ; Amoxicillin ; pharmacokinetics ; maximum entropy ; input rate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract A computer program applying the principle of maximum entropy to the analysis of drug absorption rate has been developed. Plasma concentrations of amoxicillin obtained after oral and intravenous dosing have been analysed, together with simulated data corresponding to a complex input. Amoxicillin absorption rates devised by the program were similar to those obtained by a standard deconvolution method, although they were displayed as an almost continuous profile. However, improbable fluctuations were obtained with some data sets and the fraction absorbed was underestimated by 13%. With the simulated data, the maximum entropy program did not provide a better solution than the standard deconvolution procedure, and it was sensitive to the addition of random error and to the number of samples. The maximum entropy principle, as implemented in our computer program, may not have a better performance than standard deconvolution procedures, especially in human experiments where the number of blood samples is usually limited.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00192372
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  • 27
    Digitale Medien
    Digitale Medien
    Single dose pharmacokinetics of sumatriptan in healthy volunteers (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 543-548 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Sumatriptan ; pharmacokinetics ; single dose ; bioavailability ; dose proportionality ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Sumatriptan is classified as a vascular 5HT1 receptor agonist and is effective in the acute treatment of migraine and cluster headache. Sumatriptan is available as an injection for subcutaneous administration and as a tablet for oral administration. The pharmacokinetics of sumatriptan differ depending on the route of administration. The mean subcutaneous bioavilability is 96% compared to 14% for the oral tablet. The lower bioavailability following oral administration is due mainly to presystemic metabolism. The inter-subject variability in plasma sumatriptan concentrations is greater following oral administration and a faster rate of absorption of drug into the systemic circulation is achieved following subcutaneous dosing. The pharmacokinetics of sumatriptan are linear up to a subcutaneous dose of 16 mg. Following oral dosing up to 400 mg, the pharmacokinetics are also linear, with the exception of rate of absorption, as indicated by a dose dependent increase in time to peak concentration. Sumatriptan is a highly cleared compound that is eliminated from the body primarily by metabolism to the pharmacologically inactive indoleacetic acid analogue. Both sumatriptan and its metabolite are excreted in the urine. Although the renal clearance of sumatriptan is only 20% of the total clearance, it exceeds the glomerular filtration rate, indicating that sumatriptan undergoes active renal tubular secretion. Sumatriptan has a large apparent volume of distribution (170 1) and an elimination half-life of 2 h. Oral doses of sumatriptan were administered as a solution of dispersible tablets and subcutaneous dosing was by injection into the arm. In clinical practice, sumatriptan is administered as a film coated tablet or by subcutaneous injection into the thigh.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00193709
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  • 28
    Digitale Medien
    Digitale Medien
    The pharmacokinetics of granisetron, a 5-HT3 antagonist in healthy young and elderly volunteers (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 519-520 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Granisetron ; pharmacokinetics ; elderly ; tolerance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00194344
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  • 29
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and pharmacodynamics of a single dose of recombinant human growth hormone after subcutaneous administration by jet-injection: comparison with conventional needle-injection (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 69-72 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Growth hormone ; Jet-injection ; pharmacokinetics ; pharmacodynamics ; Somatomedin C ; free fatty acids
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The pharmacokinetics and pharmacodynamics of recombinant human growth hormone (rhGH) were studied after a single subcutaneous dose given by jet-injection, and have been compared with the results obtained after conventional needle-injection. Twelve healthy male volunteers completed an open label, randomised, two-way crossover study, with a 7-day washout period between the two single sc doses. Pharmacokinetic parameters were derived from rhGH concentrations in blood samples collected regularly over 24 h after dosing on Day 1 of each period. To investigate the pharmacodynamics, additional samples were taken for the analysis of somatomedin C (IGF-I) and free fatty acids (FFA). A higher and earlier Cmax was found after jet-injection (ratio (%) jet-injected/needle-injected 124; 90%-confidence interval 108 – 142). The AUC0−∞ for rhGH were similar (ratio (%) jet-injected/needle-injected 98; 90%-confidence interval 93 – 103). Both treatments were associated with a significant and similar rise in IGF-I. Both administrations of rhGH were associated with identical rhythmical changes in FFA. The study indicates that jet-injected and needle-injected rhGH are bioequivalent with respect to the amount absorbed. The criterion for bioequivalence is not met for the rate of absorption. It is unlikely that the latter finding will influence the pharmacodynamics of rhGH, since bioequipotency was established for the effect on IGF-I generation. Jet-injection was safe in use and was generally well tolerated.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00192361
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  • 30
    Digitale Medien
    Digitale Medien
    Effects of cimetidine on pharmacokinetics and pharmacodynamics of losartan, an AT1-selective non-peptide angiotensin II receptor antagonist (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 115-119 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Losartan ; Cimetidine ; pharmacokinetics ; plasma renin activity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract This was a 2-period randomized, crossover study in 8 healthy males to determine the effects of cimetidine (400 mg q.i.d. for 6 days) on the pharmacokinetics and pharmacodynamic effects of the angiotensin II receptor antagonist, losartan (100 mg). Cimetidine increased the AUC for losartan 18% without affecting the AUC for E-3174, the active metabolite of losartan. The increase in plasma renin activity following losartan was not affected by cimetidine (maximum mean increases 12.6 and 12.1 ng Ang I·ml−1·h−1 without and with cimetidine, respectively). These results indicate that cimetidine does not appear to alter the pharmacokinetics or pharmacodynamics of losartan to a clinically significant extent.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00192369
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  • 31
    Digitale Medien
    Digitale Medien
    Lack of relationship between quinidine pharmacokinetics and the sparteine oxidation polymorphism (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 501-504 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Quinidine ; CYP2D6 ; Sparteine oxidation polymorphism ; (3S)-3OH-quinidine ; quinidine-N-oxide ; dihydroquinidine ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Quinidine is a very potent inhibitor of CYP2D6, but the role of the enzyme in the biotransformation of quinidine has only been investigated in a single in vitro study and in two small in vivo experiments, with contradictory results. The present investigation was designed to present definite evaluation of whether quinidine is metabolised by CYP2D6. Eight poor metabolizers (PM) and 8 extensive metabolizers (EM) of sparteine each took one oral dose of 200 mg quinidine. In the EM, the total clearance, the clearance via 3-hydroxylation and the clearance via N-oxidation, were 33, 3.7 and 0.23 l·h−1, respectively. In the PM, the corresponding values were 29, 3.1 and 0.18 l·h−1, respectively. There were no statistically significant differences between EM and PM in any of these pharmacokinetic parameters. It is concluded that CYP2D6 is not an important enzyme for the oxidation of quinidine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00194341
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  • 32
    Digitale Medien
    Digitale Medien
    Single-dose pharmacokinetics of nefazodone in healthy young and elderly subjects and in subjects with renal or hepatic impairment (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 221-228 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Nefazodone ; Geriatric assessment ; Hepatic cirrhosis ; Renal impairment ; pharmacokinetics ; antidepressive agents
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The single-dose pharmacokinetics of nefazodone (NEF) and its metabolites hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP) were examined in 12 healthy younger subjects ≤55 years of age (YNG), 12 elderly subjects ≥65 years of age (ELD), 12 patients with biopsy proven hepatic cirrhosis (HEP) and 12 patients with moderate renal impairment (REN), ClCR 20–60 ml·min−1. The study was of parallel group design, with each of the four subject groups receiving escalating single oral doses of 50, 100 and 200 mg of nefazodone at 1 week intervals. Serial blood samples for pharmacokinetic analysis were collected for 48 h following each dose and plasma samples were assayed for NEF, HO-NEF and mCPP by a validated HPLC method. Single oral doses up to 200 mg of nefazodone were well tolerated by all subjects. Maximum plasma levels of NEF and HO-NEF were generally attained within 1 h after administration of nefazodone. HO-NEF and mCPP plasma levels were about 1/3 and 〈1/10 those of NEF, respectively. There were no apparent gender-related pharmacokinetic differences in any group of subjects. NEF and HO-NEF pharmacokinetics were dose dependent in all four subject groups; a superproportional increase in AUC and an increase in t1/2 with increasing dose was obtained, indicative of nonlinear pharmacokinetics. Relative to normal subjects, elderly and cirrhotic subjects exhibited increased systemic exposure to NEF and HO-NEF, as reflected by AUC, at all doses of nefazodone; subjects with moderate renal impairment did not. Elderly and cirrhotic patients may require lower doses of NEF to achieve and maintain therapeutic effectiveness.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00192383
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  • 33
    Digitale Medien
    Digitale Medien
    Steady-state pharmacokinetics of nefazodone in subjects with normal and impaired renal function (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 229-235 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Nefazodone ; Renal impairment ; pharmacokinetics ; antidepressive agents
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The steady-state pharmacokinetics of nefazodone (NEF) and its metabolites hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP) were compared in subjects with normal and impaired renal function. Patients: The Study was of parallel group design which included 7 subjects with normal (NOR) renal function, CLCR≥72 ml·min−1·1.73 m−2, 6 with moderate (MOD) renal impairment, CLCR 31–60 ml·min−1·1.73 m−2 and 9 with severe (SEV) renal impairment, CLCR≤30 ml·min−1·1.73 m−2. Subjects in each renal function group received a 100-mg oral dose of nefazodone hydrochloride BID for 7 days and a single morning dose on day 8. Starting 48 h after the last 100-mg dose, 200-mg doses were administered on a similar schedule to 3, 4 and 3 subjects from each renal function group (NOR, MOD and SEV, respectively). Single trough blood samples just prior to each morning dose (Cmin) and serial samples after the dose on day 8 were obtained at each dose level for pharmacokinetic analysis. Plasma samples were assayed by a specific HPLC method for NEF, HO-NEF and mCPP. The CMIN data indicated that steady state was attained by the third day of BID administration of both the 100- and 200-mg doses of nefazodone, regardless of degree of renal function. Both NEF and HO-NEF attained steady-state Cmax within 2 h after administration of nefazodone; tmax for mCPP was less defined and more delayed. HO-NEF and mCPP plasma levels were about 1/3 and 〈1/10 those of NEF, respectively, regardless of the status of renal function. Steady-state systemic exposure of NEF and HO-NEF, as reflected by AUC and Cmax, and elimination t1/2 values did not differ significantly among renal function groups. Conclusion: The study results suggest that dose adjustments may not be necessary, but nefazodone should be used with caution in the presence of severe renal impairment.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00192384
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  • 34
    Digitale Medien
    Digitale Medien
    Relationship of changes in felodipine pharmacokinetics to haemodynamics during chronic oral treatment of congestive heart failure patients (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 203-210 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Felodipine ; pharmacokinetics ; haemodynamics ; congestive heart failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract In congestive heart failure patients the kinetics of felodipine, a dihydropyridine calcium antagonist, show interpatient differences after acute i.v. administration that disappear after 8 weeks oral treatment with a change in kinetics in the patients with the largest clearances (CL) and the smallest volumes of distribution (V SS). Pharmacokinetic and haemodynamic data were combined to construct a haemodynamic-pharmacokinetic model. This model shows that the differences between the patients in i.v. pharmacokinetics are consistent with a difference in plasma flow distribution between liver and poorly perfused tissues. In patients in whom kinetics changed, felodipine treatment is supposed to cause a redistribution of flow from liver to peripheral tissues, accompanied by a decreased work load of the heart and a larger increase in VO2max during therapy than in the other patients, whose workload increased. This suggests a better therapeutic response in the patients whose kinetics changed. As change in kinetics is related to felodipine CL and CL to liver plasma flow, felodipine CL or even indocyanine CL might be predictive for the therapeutic effect of felodipine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00192380
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  • 35
    Digitale Medien
    Digitale Medien
    The tolerability, pharmacokinetics and lack of effect on plasma cholesterol of 447C88, an AcylCoA:Cholesterol Acyl Transferase (ACAT) inhibitor with low bioavailability, in healthy volunteers (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 243-249 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cholesterol acyltransferase ; Hypocholesterolaemic ; 447C88 ; volunteers ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract 447C88 (N-Heptyl-N′-(2,4 difluoro-4-6-(2(-4-(2,2 dimethylpropyl)phenyl)ethyl)phenyl)urea) is an inhibitor of human microsomal AcylCoA:Cholesterol acyltransferase (ACAT) with an IC50 of 10.2 ng·ml−1 (23 nM). It is poorly absorbed but 5 mg·kg−1·day−1 completely abolishes the rise in plasma cholesterol in cholesterol-fed rats. In this study, twelve healthy, male volunteers received single, oral doses of 25, 50, 100, 200, 400 and 800 mg of 447C88 (n+8) or placebo (n+4) with food in a double-blind study with at least a week between occasions. The 400 mg dose was repeated after an overnight fast. Subsequently, fourteen different volunteers received a single 200 mg dose of 447C88 (n+8) or placebo (n+6) with food and, a week later, the same dose twice daily for 10 days; all doses were given with food. All doses were well tolerated with no significant changes in vital signs, full blood counts or plasma biochemical profiles. Plasma concentrations of 447C88 were unquantifiable after the fasting dose and low after all other doses. Mean Cmax and AUC were 1.8 ng·ml−1 and 9.0 ng·ml−1·h after 200 mg rising to 5.4 ng·ml−1 and 23.8 ng·ml−1·h respectively after 800 mg; t1/2 was 1.3 to 5.2 h. After 10 days dosing, plasma 447C88 concentrations were higher in the evening than the morning probably due to administration of the evening dose with more food. There were no significant changes in plasma triglcerides or total, LDL- or HDL-cholesterol after dosing with 447C88.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00192386
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  • 36
    Digitale Medien
    Digitale Medien
    Whole-blood pharmacokinetics and metabolic effects of the topical carbonic anhydrase inhibitor dorzolamide (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 453-460 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Dorzolamide ; Glaucoma ; carbonic anhydrase ; pharmacokinetics ; renal effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Following a single-dose, open-label, pilot pharmacokinetic study in six subjects, the systemic pharmacokinetics and metabolic effects of dorzolamide after topical ocular administration were investigated in a double-blind, randomised, placebo-controlled study in 12 healthy volunteers. The subjects received a controlled diet on the 5 days before treatment initiation and throughout the study. For 14 days, a bilateral q.i.d. regimen of 3% dorzolamide, consisting of approximately 7.7 μg per day (21.3 μmol) dorzolamide hydrochloride, or placebo was given. Blood and urine electrolytes and acid-base profiles were measured 1 day prior to treatment and on days 1, 7 and 14 of treatment, and 24-h urine samples were collected daily. Topically applied dorzolamide was slowly taken up in erythrocytes and eliminated with a half life of approximately 120 days. Compared to the pre-study values, no significant treatment effect was observed in either the daily profiles or the 14-day cumulative sodium, potassium and citrate excretions. Two other volunteers given acetazolamide (125 mg q.i.d.) and assessed with the identical set of observations demonstrated marked metabolic changes. In spite of the prolonged and marked inhibition of carbonic anhydrase in red blood cells by dorzolamide, clinically significant metabolic and renal effects were not observed. The ocular tolerability profile was acceptable to all subjects.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00196861
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  • 37
    Digitale Medien
    Digitale Medien
    Elimination of amrinone during continuous veno-venous haemofiltration after cardiac surgery (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 57-59 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Amrinone ; continuous veno-venous haemofiltration ; drug monitoring ; pharmacokinetics ; low cardiac output syndrom ; elimination ; renal failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract We studied the elimination of amrinone during continuous veno-venous haemofiltration (CVVHF) in three anuric patients after cardiac surgery. The patients had developed low cardiac output followed by acute prerenal failure. Plasma amrinone levels measured by HPLC were fitted to a two-compartment model. We found significant amrinone clearance, with a mean sieving coefficient (S) of 0.44%, which correlates with the protein-unbound, pharmacologically effective fraction of amrinone. The AUC of the arterial plasma concentration-time curve was decreased by 49.8%. All pharmacokinetic parameters showed wide interindividual variation. To ensure the therapeutic effect of amrinone and to avoid toxic adverse effects monitoring of plasma amrinone levels is necessary.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00202173
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  • 38
    Digitale Medien
    Digitale Medien
    Paracetamol disposition in Thai patients during and after treatment of falciparum malaria (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 65-69 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Paracetamol ; Malaria ; pharmacokinetics ; phase II conjugation ; glucuronidation ; sulphation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Investigations in animals have suggested that conjugation of paracetamol may be reduced in malaria. We have measured plasma concentrations and the urinary excretion of paracetamol and its phase II metabolites in eight Thai patients during uncomplicated falciparum malaria and in convalescence, following a 1000 mg single oral dose. The apparent oral clearance (Malaria, 3.6; Convalescence, 3.9; ml·min−1·kg−1), the elimination half-life (Malaria, 3.8; Convalescence, 3.7 h) and apparent volume of distribution (Malaria, 1.2; Convalescence, 1.2; l·kg−1) of paracetamol were similar during malaria and convalescence. In addition, the urinary excretion of paracetamol and its major phase II metabolites and their formation clearances from paracetamol were not significantly different between the two study phases. These data show that clinical malaria infection has no effect on the conjugation of paracetamol in man.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00202175
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  • 39
    Digitale Medien
    Digitale Medien
    The acetylation phenotype: does it contribute to the non-linearity of the metabolite pharmacokinetics of metamizol? (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 79-80 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Metamizol ; Acetylation phenotype ; metabolites ; pharmacokinetics ; dose-linearity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00202178
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  • 40
    Digitale Medien
    Digitale Medien
    Relative bioavailability of nicotine from a nasal spray in infectious rhinitis and after use of a topical decongestant (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 71-75 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Nicotine ; Rhinitis ; pharmacokinetics ; nasal spray ; xylometazoline ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The relative bioavailability of nicotine from a nasal spray was assessed in 15 smokers suffering a common cold and rhinitis according to generally accepted criteria. The patients were given a single dose of 2 mg nicotine from the nasal spray with and without concurrent administration of a nasal vasoconstrictor decongestant, xylometazoline, in randomised order. Control session measurements were made in the disease-free state. Applying strict bioequivalence criteria, we found that common cold/rhinitis slightly reduced the bioavailability of nicotine, both in its rate and extent; the geometric mean of the ratio of Cmax, AUC and tmax were 0.81, 0.93 and 1.36, respectively. The nasal vasoconstrictor, xylometazoline, normalised the extent of the bioavailability of nicotine, but further prolonged the time for absorption to almost twice that measured in the disease-free state, increasing the tmax ratio to 1.72. The results suggest that a minor proportion of people stopping smoking with the help of a nicotine nasal spray may experience a minor reduction in the effect of the spray during common cold/rhinitis. However, the nicotine self-titration behaviour found with most smoking cessation products (except the nicotine patch) will automatically lead to an adjustment of the dosage to achieve the desired effect.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00202176
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  • 41
    Digitale Medien
    Digitale Medien
    Effects of liver disease on the pharmacokinetics of intravenous and oral chlordesmethyldiazepam (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 265-268 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Chlordesmethyldiazepam ; Liver disease ; pharmacokinetics ; i.v./p.o. administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract We studied the pharmacokinetics of a single 0.5-mg i.v. dose of chlordesmethyldiazepam in 8 patients with liver disease and in 12 age-matched healthy controls. The kinetics were also studied of a single 1-mg oral dose in the patients with liver disease. After i.v. administration the kinetics of total chlordesmethyldiazepam in patients with liver disease differed from those in controls: elimination half-life was almost twice that in controls (395 and 204 h), as a consequence of a marked reduction in total clearance (0.13 and 0.25 ng·ml−1·h−1), whereas the apparent volume of distribution was similar in patients and controls (4.7 and 3.9 1/kg−1). The free fraction of the drug in patients was higher (5.5%) than in controls (2.9%). Correction for differences in protein binding revealed clearance in the patients was one-fifth (1.8 and 10.5 ng ml−1·kg−1) and volume of distribution one-half (65.0 and 118.4 1·kg−1) that in controls. The systemic availability of oral chlordesmethyldiazepam was high (110%) in spite of a relatively slow absorption rate. These results indicate a need for caution in the administration of chlordesmethyldiazepam to patients with liver disease.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00198309
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  • 42
    Digitale Medien
    Digitale Medien
    Effects of a finnish sauna on the pharmacokinetics and haemodynamic actions of propranolol and captopril in healthy volunteers (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 133-137 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Sauna ; Propranolol ; Captopril ; pharmacokinetics ; blood pressure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The effects of a Finnish sauna on propranolol pharmacokinetics and on the pharmacodynamics of propranolol and captopril were studied in healthy, young volunteers (2 males, 6 females) in a double-blind, cross-over trial. The subjects received single oral doses of placebo. propranolol (40 mg) or captopril (12.5 mg) in sauna and control sessions at a one-week interval. The sauna sessions consisted of three repetitive 10-min stays in a sauna (85–100°C, relative humidity 25–35%) separated by two 5-min rest periods in a cool room. Sauna bathing started 35, 50 and 65 min after ingestion of the drugs. Venous blood for plasma propranolol measurement were collected before and 15, 30, 45, 60, 75, 90 min and 2, 3, 4, 5, 7 and 24 h after drug intake. The sauna significantly increased the maximum concentration (Cmax 41 vs. 28 ng·ml−1) of propranolol and the mean plasma propranolol concentration 60 and 90 min, and 2 and 3 h after drug administration. It also significantly increased the AUC0–5h (119 vs 71 μg·h·l-1) of propranolol from 0 to 5 hours tmax, t1/2β and AUC0–24h of propranolol did not differ between the control and sauna sessions. The higher propranolol levels during and after the cessation of sauna bathing did not lead to significant changes in blood pressure or heart rate compared to the control period. Captopril had no major effects on these parameters during the post-sauna phase. The results suggest that a sauna may increase the plasma propranolol concentration, but that did not notably affect the blood pressure or heart rate in healthy, young volunteers during the post-sauna phase.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00192738
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  • 43
    Digitale Medien
    Digitale Medien
    Pharmacokinetic interactions of alcohol and acetylsalicylic acid (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 151-153 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Ethanol ; Acetylsalicylic acid ; ibuprofen ; paracetamol ; non-steroidal anti-inflammatory drugs ; interactions ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract This study assessed the influence of acetylsalicylic acid (ASA, 1.0 g), ibuprofen (0.8 g) and paracetamol (1.0 g) on the single-dose kinetics of ethanol in 12 healthy volunteers ingesting the drug and a standardised 1840-kJ breakfast 1 h before intake of ethanol. It also assessed the influence of ethanol on the single-dose kinetics of 1.0 g ASA in ten fasting healthy volunteers. Plasma concentrations of ethanol were measured by gas chromatography, and those of the drugs by liquid chromatography. There was no effect of ASA, ibuprofen or paracetamol on the single-dose kinetics of ethanol, but concurrent intake of ethanol reduced the peak concentration of ASA by 25%.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00192741
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  • 44
    Digitale Medien
    Digitale Medien
    Influence of piroxicam coadministration on pharmacodynamic parameters and the plasma concentration/effect relationship of recombinant hirudin (CGP 39393) (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 241-246 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Recombinat hirudin ; Piroxicam ; activated partial thromboplastin time ; pharmacokinetics ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Recombinant hirudins are currently under investigation for use in myocardial infarction and unstable angina. In this study the influence of piroxicam on the pharmacodynamics and pharmacokinetics of a recombinant hirudin preparation (CGP 39393) administered intravenously was determined. Twelve healthy, male volunteers received piroxicam 10 mg and matching placebo once daily for 12 days according to a double-blind, randomised cross-over design. On the 12th day, the dose of piroxicam was followed by a 6-hour infusion of hirudin 0.1 mg·kg−1·h−1. Plasma concentrations and urinary excretion of hirudin and repeated measurements of the activated partial thromboplastin time (APTT), bleeding time and platelet adhesion index were assessed up to 24 h after the start of the infusion. The maximum APTT was 83 s (placebo) and 84 s (piroxicam), 3 to 4 h after the start of the infusion, and was comparable on both study days. The AUD0–24 (APTT) came to 913 s·h·kg−1 under placebo and it was slightly increased to 1,017 s·h·kg−1 after piroxicam; the 95%-confidence interval according to MOSES ranged from 0.97 to 1.24, and the point estimator was 1.10. Bleeding time was significantly prolonged from 290 s under placebo to 345 s under piroxicam before the start of the infusion of hirudin. No further prolongation was found during or after the infusion. No change was observed in the platelet adhesion index. Responsiveness parameters according to a sigmoidal Emax-model were obtained from the hirudin-plasma concentration/effect (i.e. APTT-prolongation)-curves after placebo and piroxicam. Maximal APTT-prolongation (Emax; i.e. peak APTT minus the baseline value) was 53 s after placebo and 52 s after piroxicam. The EC50 was 34 nmol·l−1 after placebo and 40 nmol·h·l−1 after piroxicam. The AUC0 of hirudin was to 539 nmol·h·l−1·kg−1 under placebo and 557 nmol·h·l−1·kg−1 after piroxicam coadministration; the 95%- confidence interval according to MOSES ranged from 0.95 to 1.14, and the point estimator was 1.03. No period effect was detected. There were no significant differences between the other pharmacokinetic parameters except Vss, which was increased slightly from 0.23 l to 0.27 l under piroxicam. The results do not show a clinically relevant pharmacodynamic and/or pharmacokinetic interaction between hirudin and piroxicam.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00198305
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  • 45
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of fluconazole after oral administration in children with human immunodeficiency virus infection (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 291-293 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Fluconazole ; absorption ; pharmacokinetics ; HIV infection ; children
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The objective of this study was to determine the pharmacokinetics of fluconazole after oral administration in children with human immunodeficiency virus (HIV) infection. After an overnight fast, a single dose of either 2 mg·kg−1 or 8 mg·kg−1 was administered in a suspension; five children received 2 mg·kg−1 and four 8 mg·kg−1 (ages 5–13 years). Blood samples were collected at various times on day 1, and once daily on days 2–7 after the dose. Fluconazole serum concentrations were measured by gas chromatography. At the dose of 2 mg·kg−1, the Cmax, AUC (0–∞), and t1/2 ranged from 2.3–4.4 μg·ml−1, 84.9–136 μg·h·ml−1, and 19.8–34.8 h, respectively. At the dose of 8 mg·kg−1 the Cmax, AUC (0–∞), and t1/2 ranged from 5.4–12.1 μg·ml−1, 330–684 μgh·ml−1, and 25.6–42.3 h, respectively. When compared with published data in healthy adults, fluconazole achieved similar serum concentrations in the present group of children, indicating a nearly complete degree of absorption.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00198314
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  • 46
    Digitale Medien
    Digitale Medien
    Humoral and haemodynamic effects of idrapril calcium, the prototype of a new class of ACE-inhibitors, in essential hypertensive patients (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 339-343 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Idrapril ; ACE-inhibition ; Hypertension ; essential ; active renin ; angiotensin II ; blood pressure ; pharmacodynamics ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blood pressure, heart rate, plasma idrapril serum ACE, active renin and angiotensin II were measured at timed intervals for 24 hours after dosing. Plasma idrapril reached a peak after 2 hours (3.01 μ·ml−1), and by 12 hours the compound had al most disappeared (67 ng·ml−1). Derived t1/2 was 1.4–2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol−1·min−1·ml] and angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 12 hours) pg·ml−1] for up to 12 h, while active renin rose up to 24 h [from 12.3 to 20.1 (after 8 hours) and 17.5 (after 24 hours) pg·ml−1]. Compared to placebo, idrapril calcium significantly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg) up to 24 hours (idrapril calcium 142/91 mmHg; placebo: 155/97 mmHg), and upright blood pressure starting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essential hypertension, with a hypotensive action for up to 24 h.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00194948
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  • 47
    Digitale Medien
    Digitale Medien
    Relative bioavailability of cyclosporin from conventional and microemulsion formulations in heart-lung transplant candidates with cystic fibrosis (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 285-289 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cyclosporin ; Cystic fibrosis ; pharmacokinetics ; bioavailability ; formulation ; transplantation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Patients with cystic fibrosis absorb cyclosporin poorly and erratically. We have compared the relative bioavailability of cyclosporin from conventional and microemulsion formulations in 5 adult heart-lung transplant candidates with cystic fibrosis. Relative bioavailability was compared at two dose levels (200 mg and 800 mg). A randomized 4-period cross-over study was performed with at least a 7 days washout period between each single dose pharmacokinetic study. Blood cyclosporin concentrations were measured by a selective monoclonal antibody-based radioimmunoassay. The bioavailability of cyclosporin from the microemulsion formulation was 1.84 (95% C.I. 1.05 to 3.22; P−0.04) and 2.09 (95% C.I. 0.95 to 4.61; P−0.06) times higher compared with the conventional formulation at 200 mg and 800 mg respectively. Cmax following the microemulsion formulation was 3.38 (C.I. 1.14 to 10.59; P−0.04) and 2.77 (C.I. 1.48 to 5.19; P−0.01) times higher compared with the conventional formulation at 200 mg and 800 mg respectively. The higher Cmax following the microemulsion formulation was accompanied by shorter tmax. An enhancement of cyclosporin absorption with the microemulsion formulation was demonstrated in each patient for at least one dose level. We conclude that rate and extent of cyclosporin absorption from the microemulsion formulation is greater compared with the conventional formulation in patients with cystic fibrosis. The potential therapeutic and economic benefits of the micro-emulsion formulation should be evaluated in cystic fibrosis patients following heart-lung transplantation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00198313
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  • 48
    Digitale Medien
    Digitale Medien
    Pharmacokinetic-pharmacodynamic (PK-PD) modeling for a new antihypertensive agent (neutral metalloendopeptidase inhibitor SCH 42354) in patients with mild to moderate hypertension (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 351-359 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Atrial natriuretic peptide ; Hypertension ; SCH 42354 ; blood pressure ; neutral metalloendopeptidase ; pharmacodynamics ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract SCH 42354, a neutral metalloendopeptidase (NEP) inhibitor, is the pharmacologically active form of the prodrug SCH 42495. It exerts antihypertensive effects by potentiating atrial natriuretic peptide (ANP) activity through inhibition of its hydrolysis by NEP. The objective of this study was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of SCH 42354 in hypertensive males. SCH 42495 12.5 to 400 mg was administered orally to hypertensive men twice daily in a double-blind, placebo controlled multiple-dose parallel group design. Plasma SCH 42354 concentration and diastolic blood pressure (DBP) data were used to develop a PK-PD model using two approaches. In the first (non-integrated) approach, the “link” model was used to predict effect-site concentrations, and was applied to data obtained at the 300 and 400 mg BID doses only; data at the other (lower) doses were not amenable to modeling because of high variability. Effect-site concentration and DBP data were then fit to a sigmoid Emax PD model. For the 300 mg BID dose, PD parameters were: maximum effect (Emax), 8.1mmHg; no-drug effect (Eo), 3.6 mmHg; concentration corresponding to 50% of maximum response (EC50), 0.87 μg·ml−1; and gamma, 3.9. In the second (time-integrated) approach, plasma SCH 42354 concentration and effect data obtained over the entire dose range were integrated with respect to time. Average plasma concentration and DBP data were then fit to a simple Emax PD model. PD parameters obtained over the dose range were: Emax, 10.3 mmHg; Eo, 2.0 mmHg; and EC50, 0.7 μg·ml−1. These were similar to the estimates obtained from the first approach, demonstrating that the integrated (average) data allow PK-PD modeling over the (entire) dose range. The analysis showed that, at steady-state, a 400 mg BID dose of SCH 42495 produced an approximate 10 mmHg decrease in DBP in hypertensive males; the average plasma SCH 42354 concentration attained at this dose was approximately 1.8 μg·ml−1.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00194950
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  • 49
    Digitale Medien
    Digitale Medien
    The effect of pH on the buccal and sublingual absorption of captopril (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 373-379 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Captopril ; sublingual ; pharmacokinetics ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The effect of pH on the buccal and sublingual absorption of captopril was evaluated using in vitro techniques and human studies. Partitioning of captopril into n-octanol was lowest over the pH range 5 to 8 and highest at pH values 3, 4 and 9. Using the buccal absorption technique, the partitioning of captopril (2 mg) was examined in six healthy male volunteers from buffered solutions (pH 3, 4, 5, 6, 7, 8, and 9). Lowest buccal partitioning occurred at pH 3 while maximal buccal partitioning occurred at pH 7. These data clearly indicated that the buccal absorption of captopril did not obey the classical pH/partition hypothesis suggesting that mechanisms other than passive diffusion were involved in its absorption. Captopril pharmacokinetic and pharmacodynamic parameters were determined after administration of buffered sublingual captopril (pH 7, optimal pH for absorption as determined from the buccal partitioning data) and unbuffered sublingual captopril. The study was performed in eight healthy volunteers in a randomised single-blind cross-over fashion. The tmax for captopril was found to be approximately 11 minutes earlier after buffered versus unbuffered sublingual administration and AUC0–30 min increased by approximately 30% in the case of buffered captopril. Cpmax, AUC0–180 min and relative bioavailability did not differ between the buffered and unbuffered administration. Pharmacodynamic parameters (BP, heart rate and plasma renin activity) did not differ significantly between buffered and unbuffered sublingual administration. The increased rate of captopril absorption after buffered sublingual administration was small and is likely to offer little therapeutic advantage over conventional sublingual formulation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00194953
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  • 50
    Digitale Medien
    Digitale Medien
    Plasma and red blood cell pharmacokinetics of pimobendan enantiomers in healthy Chinese (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 537-542 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Pimobendan ; enantiomers ; pharmacokinetics ; stereoselectivity ; demethyl pimobendan ; metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The pharmacokinetics of enantiomers of pimobendan and their demethylated metabolites in plasma and red cells were studied in 8 normal healthy volunteers. After racemic pimobendan 5 mg IV, the plasma concentration-time curve followed a two-compartment open-model with elimination half-lives of 1.81 h and 1.86 h for (+)- and (−)-pimobendan, respectively. The clearances and volumes of distribution postequilibrium were 13.5 ml · min−1 · kg−1, 14.4 ml · min−1 · kg−1; 1.74 l · kg−1 and 2.34 l · kg−1 for (+)- and (−)-pimobendan, respectively. Plasma protein binding (n=3) of (+)-, (−)-pimobendan, (+)- and (−)-demethylated metabolites was 97.6, 97.6, 92.2 and 92.5%, respectively. The plasma concentration-time curve also followed a two-compartment open model after oral administration of 7.5 mg racemic pimobendan. The absolute bioavailabilities of (+)- and (−)-pimobendan were 0.51 and 0.55. Peak levels of (+)-and (−)-pimobendan, both at 1.2 h, were 15.8 and 16.8 ng · ml−1, respectively. The (+)- and (−)-pimobendan concentrations in red cells were determined and their pharmacokinetics were estimated using red blood cell data. Interesting phenomena were observed: the peak concentrations of (+)- and (−)-pimobendan in red blood cells were about 5.5- and 9.2-times higher than in plasma, and the AUCs were correspondingly elevated. The volume of distribution of the central compartment of (−)-pimobendan in red cell was significantly smaller than that of (+)-pimobendan. (0.24 vs. 0.42 l · kg−1.) Similar phenomena were found after IV administration. These all indicated stereoselective partitioning or distribution of (−)-pimobendan into red cells. Since the elimination half-life of (+)- and (−)-pimobendan in red cells was similar (3.07 vs 2.97 h), the highly significant difference in clearance between (+)- and (−)-pimobendan (3.7 vs 2.3 ml · min−1 · kg−1) was solely due to the stereoselective distribution of (−)-pimobendan into the red blood cells. This stereoselective property of the (−)-isomer may be the explanation of a previous report that (−)-pimobendan produced a 1.5-times larger contractile force in detergent-skinned preparations of cardiac muscle from guinea pig and dog than the (+)-isomer.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00193708
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  • 51
    Digitale Medien
    Digitale Medien
    Olfactory responses of the parasitoidDiaeretiella rapae (Hymenoptera: Aphidiidae) to odor of plants, aphids, and plant-aphid complexes (1995)
    Springer
    Journal of chemical ecology 21 (1995), S. 407-418 
    Details
    ISSN: 1573-1561
    Schlagwort(e): Kairomone ; biological control ; cabbage ; wheat ; Diuraphis noxia ; Brevicoryne brassicae ; olfactometer ; infochemical ; preference ; host plants
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Diaeretiella rapae (M'Intosh) (Hymenoptera: Aphidiidae) is a parasitoid of several aphid species, including the Russian wheat aphid (RWA),Diuraphis noxia (Mordvilko), and the cabbage aphid (CA).Brevicoryne brassicae (L.). The response of matedD. rapae females to odors from wheat, cabbage, and plant-host complexes was investigated using a four-choice olfactometer. Experienced parasitoids, but not inexperienced females, responded positively to odors of the wheat-RWA complex in a no-choice test. In choice tests, experienced parasitoids did not respond to odors of uninfested cabbage and wheat leaves, but did respond positively to aphid-infested plants and to aphids alone. The response ofD. rapae to the cabbage-CA complex and to CA alone was significantly greater than to the wheat-RWA complex and RWA alone, suggesting an innate odor preference for crucifer-feeding aphids.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02036738
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  • 52
    Digitale Medien
    Digitale Medien
    Effects of ambient air pollution on wheat and rice yield in Pakistan (1995)
    Springer
    Water, air & soil pollution 85 (1995), S. 1311-1316 
    Details
    ISSN: 1573-2932
    Schlagwort(e): Pakistan ; air pollution ; ozone ; nitrogen dioxide ; rice ; wheat ; filtration ; yield
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Energietechnik
    Notizen: Abstract Open-top chambers ventilated with ambient or chiarcoal-filtered air were used to assess the impact of air pollution on the yield of local cultivars of wheat and rice, at a site on the outskirts of Lahore. At this location, 6-h mean O3 concentrations reach 60 ppb in certain months, and annual mean NO2 concentrations are 20–25 ppb. The experiments showed significant yield reduction in two successive seasons which ranged from 33% to 46% in wheat and from 37% to 51% in rice. The major yield parameter affected was the number of ears or panicles per plant, although there was also evidence of small effects on 1000 grain weight and on the number of grains per ear/panicle. These results have significance in terms of the maintenance of agricultural yields as pollution emissions rise in south and south-east Asia.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00477163
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  • 53
    Digitale Medien
    Digitale Medien
    Ozone effects on dry matter partitioning and chlorophyll fluorescence during plant development of wheat (1995)
    Springer
    Water, air & soil pollution 85 (1995), S. 1461-1466 
    Details
    ISSN: 1573-2932
    Schlagwort(e): ozone ; wheat ; Triticum aestivum ; growth ; senescence ; biomass partitioning ; photosynthesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Energietechnik
    Notizen: Abstract In closed-chamber fumigation experiments dry matter partitioning and chlorophyll fluorescence of wheat were studied, analysing the effects of ozone during different stages of plant development. Ozone causes enhanced leaf senescence, leading to a loss of green leaf area and, consequently to a decreased supply of assimilates, affecting (in increasing order of severeness) stem, ear and grain productivity because of reduced storage pools for translocation. Leaves of plants before shooting stage were most sensitive but the lack of green leaf area after ear emergence had the most pronounced effects on grain yield. Measurements of photochemical capacity showed that evidence for negative ozone effects could be found in changes of chlorophyll fluorescence parameters in leaf sections not yet showing visible ozone injury. Negative effects on photosynthesis were more distinct with increasing accumulated ozone dose, with increasing age of leaf tissue and with increasing ozone sensitivity of the cultivar. The changes in chlorophyll fluorescence are most likely to be explained by a decreased pool size of plastoquinones caused by ozone.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00477187
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  • 54
    Digitale Medien
    Digitale Medien
    Quantifying the fine scale (1km × 1km) exposure, dose and effects of ozone: Part 2 estimating yield losses for agricultural crops (1995)
    Springer
    Water, air & soil pollution 85 (1995), S. 1485-1490 
    Details
    ISSN: 1573-2932
    Schlagwort(e): Ozone ; wheat ; areal interpolation ; economics ; yield losses ; critical levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Energietechnik
    Notizen: Abstract In Britain wheat is an important crop accounting for 41% of the total cereal production. In this study ozone concentrations for 1989 estimated as described in Part 1 of the paper are integrated with the estimated wheat distribution to derive a detailed estimate of the impact of ozone on wheat yields at a fine spatial scale (1km × 1km). These data provide estimates for calculating regional and national yield losses. The methodology can be applied to other crop species. Recent research on a range of crops has established relationships between the economic yield loss for certain crops, including wheat, and ozone exposure. Exposure is described as the accumulated exposure above a threshold experienced during the daylight hours (AOT). Critical AOT values are derived from yield exposure relationships which show linear reductions of yield loss with increasing ozone concentrations. This study has made use of land cover data from remotely sensed imagery at 25m resolution and nationally collected agricultural statistics for counties. These data were combined using an areal interpolation technique to provide more spatially articulate estimates of the location and intensity of wheat production. The results demonstrate the economic importance of ozone as a pollutant. Wheat yield losses attributed to ozone vary between different parts of the country but, for years when ozone levels are high, yield losses are likely to be significant in some areas.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00477191
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  • 55
    Digitale Medien
    Digitale Medien
    A Zea mays GTP-binding protein of the ARF family complements an Escherichia coli mutant with a temperature-sensitive malonyl-coenzyme A:acyl carrier protein transacylase (1995)
    Springer
    Plant molecular biology 27 (1995), S. 629-633 
    Details
    ISSN: 1573-5028
    Schlagwort(e): GTP binding ; ADP ribosylation ; Zea mays ; Escherichia coli ; fatty acid biosynthesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract In an attempt to isolate a plant malonyl-coenzyme A:acyl carrier protein transacylase cDNA clone, by direct genetic selection in an Escherichia coli fabD mutant (LA2-89) with a maize cDNA expression library, a Zea mays cDNA clone encoding a GTP-binding protein of the ARF family was isolated. Complementation of a mutation affecting bacterial membrane lipid biosynthesis by a plant ARF protein, could indicate the existence of as yet unidentified bacterial equivalents of this ubiquitous eucaryotic GTP-binding protein.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00019329
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  • 56
    Digitale Medien
    Digitale Medien
    The involvement of Opaque 2 on β-prolamin gene regulation in maize and Coix suggests a more general role for this transcriptional activator (1995)
    Springer
    Plant molecular biology 27 (1995), S. 1015-1029 
    Details
    ISSN: 1573-5028
    Schlagwort(e): β-prolamin ; Coix lacryma-jobi ; different O2-binding sites ; Opaque 2 ; transcriptional regulation ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The maize opaque 2 (o2) mutation is known to have numerous pleiotropic effects. Some polypeptides have their expression depressed while others are enhanced. The best characterized effects of the o2 mutation are those exerted on endosperm genes encoding the storage protein class of the 22 kDa α-zeins and the ribosome inactivating protein b-32. The Opaque 2 (O2) locus encodes a basic domain-leucine zipper DNA-binding factor, O2, which transcriptionally regulates these genes. In the maize-related grass Coix lacryma-jobi, an O2-homologous protein regulates the 25 kDa α-coixin gene family. We show in this paper that O2 transcriptionally regulates the structurally and developmentally different class of the β-prolamins. A new O2-binding box was identified in β-prolamin genes from maize and Coix that, together with the boxes previously identified in other endosperm expressed genes, forms a curious collection of O2 cis elements. This may have regulatory implications on the role of O2 in the mechanism that controls coordinated gene expression in the developing endosperm. Considering that the O2 locus controls at least three distinct classes of genes in maize endosperm, we propose that the O2 protein may play a more general role in maize endosperm development than previously conceived.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00037028
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  • 57
    Digitale Medien
    Digitale Medien
    Molecular cloning, characterization and expression of an elongation factor 1α gene in maize (1995)
    Springer
    Plant molecular biology 29 (1995), S. 611-615 
    Details
    ISSN: 1573-5028
    Schlagwort(e): elongation factor 1α ; EF-1α ; Zea mays ; cDNA sequence ; gene
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract A cDNA (zmEF1A) and the corresponding genomic clone (zmgEF1A) of a member of the gene family encoding the α subunit of translation elongation factor 1 (EF-1α) have been isolated from maize. The deduced amino acid sequence is 447 residues long interrupted by one intron. Southern blot analysis reveals that the cloned EF-1α gene is one member out of a family consisting of at least six genes. As shown by northern hybridizations in leaves the mRNA level increases at low temperature whereas time-course experiments over 24 h at 5°C show that in roots the overall mRNA level of EF-1α is transiently decreased. These results indicate that the expression of EF-1α is differently regulated in leaves and roots under cold stress.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00020988
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  • 58
    Digitale Medien
    Digitale Medien
    Developmental, circadian and light regulation of wheat ferredoxin gene expression (1995)
    Springer
    Plant molecular biology 27 (1995), S. 293-306 
    Details
    ISSN: 1573-5028
    Schlagwort(e): ferredoxin ; PetF gene ; circadian rhythm ; light regulation ; wheat ; Triticum aestivum
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract A genomic clone encoding the precursor of wheat leaf ferredoxin has been isolated and characterised. The uninterrupted PetF gene encodes a polypeptide of 143 amino acid residues, consisting of an N-terminal presequence of 46 amino acid residues and a mature polypeptide of 97 amino acid residues. Southern blot analysis suggests that six copies of the PetF gene are present in the wheat haploid genome. Northern blot analysis has shown that the genes are both developmentally and light regulated in wheat seedlings and provides evidence that a circadian rhythm regulates the steady-state levels of ferredoxin transcripts. The intact wheat gene and several chimeric constructs, containing portions of the 5′-upstream region fused to the β-glucuronidase reporter gene, have been introduced into tobacco plants, but levels of β-glucuronidase activity above background were not detected, suggesting that the 5′-upstream region is unable to function as a promoter in tobacco plants.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00020184
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  • 59
    Digitale Medien
    Digitale Medien
    Multiple cDNAs of wheat voltage-dependent anion channels (VDAC): Isolation, differential expression, mapping and evolution (1995)
    Springer
    Plant molecular biology 29 (1995), S. 109-124 
    Details
    ISSN: 1573-5028
    Schlagwort(e): cDNAs ; expression ; mapping porin ; VDAC ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The mitochondrial outer membrane of eukaryotic cells contains voltage-dependent anion channels (VDAC) also termed porins. Three cDNAs from wheat (Triticum aestivum) were isolated and sequenced (Tavdac 1–3). They share 65% similarity of their amino acid sequences, and therefore they probably represent isoforms. The deduced amino acid sequence of one of the cDNAs was found to be identical to the purified VDAC protein from wheat mitochondria [8]. Secondary structure analysis of the deduced amino acid sequences of the three vdac cDNAs revealed a characteristic α helix at their N-terminal and β-barrel cylinders characteristic of VDAC channels. The Tavdac cDNAs are differentially expressed in meristematic tissues. The transcript levels of Tavdac 1 in all wheat tissues is at least 2.5-fold higher than Tavdac 2 and Tavdac 3. Tavdac 2 has a low level of expression in all floral tissues whereas Tavdac 3 is highly expressed in anthers. This is the first report on differential expression of vdac genes in plants. The Tavdac genes have been mapped on the wheat genome. Tavdac 1 is located on the long arm of chromosome 5, Tavdac 2 on the long arm of chromosome 1 and Tavdac 3 on the long arm of chromosome 3. A phylogenetic reconstruction indicates that vdac genes underwent numerous duplication events throughout their evolution. All duplications occurred after the separation of plants from animals and fungi, and no orthologous genes are shared among phyla. Within plants, some of the vdac gene duplications probably occurred before the monocotydelon-dicotydelon split.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00019123
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  • 60
    Digitale Medien
    Digitale Medien
    The maize GapC4 promoter confers anaerobic reporter gene expression and shows homology to the maize anthocyanin regulatory locus C1 (1995)
    Springer
    Plant molecular biology 29 (1995), S. 1293-1298 
    Details
    ISSN: 1573-5028
    Schlagwort(e): anaerobiosis ; BMS cells ; glyceraldehyde-3-phosphate dehydrogenase ; transient gene expression ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The cytosolic glyceraldehyde-3-phosphate dehydrogenase (GapC) gene family of maize is differentially expressed in response to anaerobic stress. While GapC1 and GapC2 are downregulated, GapC3 and GapC4 are anaerobically induced. We have sequenced and analyzed a 3073 bp promoter fragment of GapC4. The promoter confers anaerobic induction of a reporter gene construct in a transient gene expression system in maize. Deletion analysis of the GapC4 promoter revealed a 270 bp long DNA region required for anaerobic induction. This region contains sequence motifs resembling the cis-acting sequences of the anaerobically induced maize Adh1 and Adh2 genes. Furthermore, the 3073 bp GapC4 promoter fragment displays homology to long terminal repeats of maize retrotransposons and to the 3′ region of the maize anthocyanin regulatory locus C1.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00020469
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  • 61
    Digitale Medien
    Digitale Medien
    Molecular cloning and characterization of six cDNAs expressed during glucose starvation in excised maize (Zea mays L.) root tips (1995)
    Springer
    Plant molecular biology 28 (1995), S. 473-485 
    Details
    ISSN: 1573-5028
    Schlagwort(e): carbon catabolite repression ; cDNA ; gene expression ; stress-induced genes ; glucose-starvation ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract In order to isolate glucose-starvation-related cDNAs in maize (Zea mays L.) root tips, a cDNA library was constructed with poly(A)+ mRNA from 24 h starved root tips. After differential screening of the library, we isolated six different cDNAs (named pZSS2 and pZSS7) which were expressed during glucose starvation. Time course analysis revealed that maximum expression of five of these genes occurs 30 h after the onset of the starvation treatment. On the contrary, the expression of mRNAs corresponding to pZSS4 was maximal at an early stage of starvation and then dramatically decreased. The expression of this gene did not seem to be specific for glucose starvation. The pattern of induction of the genes corresponding to pZSS2, pZSS3, pZSS5, pZSS6 and pZSS7 revealed that non-metabolizable sugars such as L-glucose and mannitol induce mRNA transcription similarly to glucose starvation. When D-glucose or any other metabolizable sugar was supplied, the level of transcripts was reduced. Nucleotide sequence analyses of the six cDNAs allowed identification of five of them by comparison with sequence data bases. The protein encoded by clone pZSS2 is analogous to a wound-induced protein from barley. Clones pZSS4 to pZSS7 encode, respectively, a transmembrane protein, a cysteine protease, a metallothionein-like protein and a chymotrypsin/subtilisin-like protease inhibitor. Clone pZSS3 shares no significant homology with any known sequence.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00020395
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  • 62
    Digitale Medien
    Digitale Medien
    Intron-dependent transient expression of the maize GapA1 gene (1995)
    Springer
    Plant molecular biology 28 (1995), S. 667-676 
    Details
    ISSN: 1573-5028
    Schlagwort(e): gene expression ; promoter ; glyceraldehyde-3-phosphate dehydrogenase ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Transient expression experiments show that the maize GapA1 promoter exhibits a requirement for sequences contained within intron 1 and surrounding exon border regions for expression in maize Black Mexican Sweet cells. Maize GapA1-promoter constructs lacking intron 1 are inactive. Intron 1 and its exon border sequences, when reintroduced into constructs lacking introns, restore gene activity whereas intron 2 and its exon borders to not. The minimal promoter so defined encompasses roughly 250 bp upstream of the in vivo transcription start and appears also to include intron 1. An octameric sequence was identified in intron 1 of maize GapA1 which is similar to sequence motifs found in other maize introns known to increase transient expression. Partial restoration of gene expression in GapA1 constructs lacking intron 1 was achieved through insertion of the identified octameric sequence.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00021192
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  • 63
    Digitale Medien
    Digitale Medien
    PCR-generated cDNA library of transition-stage maize embryos: cloning and expression of calmodulin genes during early embryogenesis (1995)
    Springer
    Plant molecular biology 27 (1995), S. 105-113 
    Details
    ISSN: 1573-5028
    Schlagwort(e): calmodulin ; cDNA library ; embryogenesis ; PCR ; transition stage ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract One hundred maize zygotic embryos microdissected at the transition stage were used to construct a cDNA library after non-selective PCR (NS-PCR) amplification of whole cDNA populations. The library contains 2.3 × 105 recombinants and two different calmodulin cDNAs were cloned using a heterologous probe from petunia. Calmodulin expression was confirmed throughout maize embryogenesis at the mRNA, amplified cDNA and protein levels. Sequence analysis suggests a maize origin for both clones and negligible nucleotide changes linked to PCR. This library is the first described for early plant embryos and represents a breakthrough to isolate genes involved in embryo differentiation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00019182
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  • 64
    Digitale Medien
    Digitale Medien
    Evidence for the thiamine biosynthetic pathway in higher-plant plastids and its developmental regulation (1995)
    Springer
    Plant molecular biology 29 (1995), S. 809-821 
    Details
    ISSN: 1573-5028
    Schlagwort(e): Zea mays ; thiamine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Thiamine or vitamin B-1, is an essential constituent of all cells since it is a cofactor for two enzyme complexes involved in the citric acid cycle, pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. Thiamine is synthesized by plants, but it is a dietary requirement for humans and other animals. The biosynthetic pathway for thiamine in plants has not been well characterized and none of the enzymes involved have been isolated. Here we report the cloning and characterization of two cDNAs representing members of the maize thi1 gene family encoding an enzyme of the thiamine biosynthetic pathway. This assignment was made based on sequence homology to a yeast thiamine biosynthetic gene and by functional complementation of a yeast strain in which the endogenous gene was inactivated. Using immunoblot analysis, the thi1 gene product was found to be located in a plastid membrane fraction. RNA gel blot analysis of various tissues and developmental stages indicated thi1 expression was differentially regulated in a manner consistent with what is known about thiamine synthesis in plants. This is the first report of cDNAs encoding proteins involved in thiamine biosynthesis for any plant species.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00041170
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  • 65
    Digitale Medien
    Digitale Medien
    Manipulating cytoplasmic pH under anoxia: A critical test of the role of pH in the switch from aerobic to anaerobic metabolism (1995)
    Springer
    Planta 195 (1995), S. 324-330 
    Details
    ISSN: 1432-2048
    Schlagwort(e): Anoxia ; Biochemical pH-stat ; Cytoplasmic pH ; Ethanol production ; Pyruvate decarboxylase ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Ethanol production by maize (Zea mays L.) root tips, measured by an enzymic assay of the suspending medium, was correlated with changes in the cytoplasmic pH, determined by in-vivo 31P nuclear magnetic resonance (NMR) spectroscopy, following the onset of anoxia. Strong evidence for the role of the cytoplasmic pH in triggering the switch to ethanol production under anoxia was obtained by: (i) varying the pH of the suspending medium between pH 4 and pH 10; and (ii) using the permeant weak base methylamine to combat the acidification of the cytoplasm induced by the anoxic conditions. Experimentally, it proved to be much easier to manipulate the cytoplasmic pH under anoxia after the pH had stabilised, rather than during the initial rapid acidification that occurred following the onset of anoxia, and in the presence of methylamine, it was possible to impose a normal aerobic cytoplasmic pH value on tissue that was metabolising anaerobically. By this means it was possible to demonstrate the reversibility of the pH effect on ethanol production under anoxia and thus to provide good evidence in support of the biochemical pH-stat model of the anoxic response. The NMR measurement of the cytoplasmic pH in the presence of methylamine was achieved by using a manganese pretreatment technique to eliminate interference between the cytoplasmic and vacuolar Pi signals, and it seems likely that the experimental approach used here will have further applications in studies of the metabolic response to anoxia.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00202588
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  • 66
    Digitale Medien
    Digitale Medien
    Transport and dynamics of molecules dissolved in maize root cortex membranes (1995)
    Springer
    The journal of membrane biology 143 (1995), S. 19-28 
    Details
    ISSN: 1432-1424
    Schlagwort(e): Plant membrane ; Lipid domain ; Fluorescence photobleaching recovery ; Electron paramagnetic resonance ; Temperature stress ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Translational diffusion of a fluorescent sterol probe was measured in the plasma membranes of protoplasts isolated from cortical cells of the primary root of maize seedlings. The apparent lateral diffusion coefficient was typically observed to be nearly insensitive to temperature, while the mobile fraction increased with increasing temperature. These fluorescence photobleaching recovery (FPR) measurements were compared with the electron paramagnetic resonance (EPR) spectra of the methyl ester of 13-doxyl palmitic acid in membranes of corn root tissue in situ. The complex spectra observed with this probe were analyzed as weighted sums of simpler spectra of various order parameters and rotational correlation times. The reconstituted spectra calculated from the model show that EPR also detects a mobile (less ordered, fluid) fraction, distinguished by the order parameter S=0.1 to 0.2, which becomes more abundant as temperature increases and is qualitatively comparable to the mobile fraction determined by the FPR method. The observed results on the mobile fractions and the diffusion rates for translational (FPR) as well as rotational (EPR) motions are interpreted in terms of membrane organization, thus providing information on the population and structural patterns of the coexisting domains with a special emphasis on the response of the membrane to temperature changes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00232520
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  • 67
    Digitale Medien
    Digitale Medien
    Detection of the apomictic mode of reproduction in maize-Tripsacum hybrids using maize RFLP markers (1995)
    Springer
    Theoretical and applied genetics 90 (1995), S. 1198-1203 
    Details
    ISSN: 1432-2242
    Schlagwort(e): Diplospory ; RFLP ; Bulk-segregant analysis ; Genome similarity ; Intergeneric hybrids ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Polyploid plants in the genus Tripsacum, a wild relative of maize, reproduce through gametophytic apomixis of the diplosporous type, an asexual mode of reproduction through seed. Moving gene(s) responsible for the apomictic trait into crop plants would open new areas in plant breeding and agriculture. Efforts to transfer apomixis from Tripsacum into maize at CIMMYT resulted in numerou intergeneric F1 hybrids obtained from various Tripsacum species. A bulk-segregant analysis was carried out to identify molecular markers linked to diplospory in T. dactyloides. This was possible because of numerous genome similarities among related species in the Andropogoneae. On the basis of maize RFLP probes, three restriction fragments co-segregating with diplospory were identified in one maize-Tripsacum dactyloides F1 population that segregated 1∶1 for the mode of reproduction. The markers were also found to be linked in the maize RFLP map, on the distal end of the long arm of chromosome 6. These results support a simple inheritance of diplospory in Tripsacum. Manipulation of the mode of reproduction in maize-Tripsacum backcross generations, and implications for the transfer of apomixis into maize, are discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00222943
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  • 68
    Digitale Medien
    Digitale Medien
    Developmental SEM observations on an extracellular matrix in embryogenic calli ofDrosera rotundifolia andZea mays (1995)
    Springer
    Protoplasma 186 (1995), S. 45-49 
    Details
    ISSN: 1615-6102
    Schlagwort(e): Drosera rotundifolia ; Embryogenic callus ; Extracellular matrix ; Scanning electron microscopy ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Primary embryogenic callus ofDrosera rotundifolia and long-term cultured embryogenic callus ofZea mays possess a conspicuous extracellular matrix (ECM) around and between embryogenic cells. The structural arrangement of ECM depends on the developmental stage of the embryogenic cells. Single embryoid cells were covered with, and connected by net-like material. However, surface cells of young globular embryoids were covered with a coherent layer of ECM which forms bridges with net-like material between the cells which was gradually reduced to coarse strands. When protodermis was formed on the surface of globular embryoids, the ECM disappeared completely. The ECM network was never observed on the surface of heart- and torpedo-shaped embryoids. Safranine (especially 0.1%) stabilized the structure of ECM. Digestion with pronase E and proteinase K indicated that the ECM contains proteinaceous components. Similar developmental patterns of ECM were observed in dicotyledonous and monocotyledonous examples. The ECM represents a stable morphological structure even during long-term embryogenic culture in maize.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01276934
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  • 69
    Digitale Medien
    Digitale Medien
    From in vitro fertilization to early embryogenesis in maize (1995)
    Springer
    Protoplasma 187 (1995), S. 3-12 
    Details
    ISSN: 1615-6102
    Schlagwort(e): Gamete protoplasts ; In vitro fertilization ; Early embryogenesis ; Developmental mutations ; Polymerase chain reaction ; cDNA libraries ; Gene cloning ; Angiosperm ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The development of in vitro fertilization methods in plants, the characterization of developmental mutants, and the adaptation of molecular biology techniques to construct cDNA libraries from minute samples, all represent important recent technical break-throughs. They allow the study of fertilization and early embryogenesis at a molecular level and considerable improvement in the under-standing of higher plant reproduction can be predicted over the next few years. Important biological questions, such as polyspermy, gamete fusion physiology, asymmetrical cell division, embryo axis formation, can now be addressed experimentally in maize, which appears as a major study model in this area.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01280227
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  • 70
    Digitale Medien
    Digitale Medien
    uidA gene transfer and expression in maize microspores using the biolistic method (1995)
    Springer
    Protoplasma 187 (1995), S. 138-143 
    Details
    ISSN: 1615-6102
    Schlagwort(e): Biolistics ; Microspores ; GUS-expression ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The ability to recover male gametophyte derived plants, which is necessary to get transformed haploid plants, was verified for a hybrid of maize. Using the isolated microspore culture technique, a 9 × 10−5 plant regeneration frequency was obtained. Maize microspores were bombarded with tungsten particles using a PDS He/1000 apparatus. GUS expression in the microspores was maximum with 1.1 μm diameter tungsten microprojectiles for 1100 and 1350 psi helium pressures at a 6 cm distance between the launch point and the target cells. Increasing the amount of DNA coated on the microparticles from 1.66 to 4 μg DNA/mg of particles allowed a two-fold and four-fold increase of the GUS-expressing microspore frequency for 1100 and 1350 psi helium pressure bombardment, respectively. Optimal concentration of solidifying agent in the bombardment support culture medium was found to be 1%. Cell density ranging from 25000 microspores/bombardment to 100000 microspores/bombardment did not affect the frequency of GUS-expressing microspores. Using these optimal conditions, the maximum frequency of GUS-expressing microspores was found to be about 9 × 10−4, while maintaining an embryo formation frequency about 5 × 10−4.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01280242
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  • 71
    Digitale Medien
    Digitale Medien
    Distribution of pectins in cell walls of maize coleoptiles and evidence against their involvement in auxin-induced extension growth (1995)
    Springer
    Protoplasma 188 (1995), S. 213-224 
    Details
    ISSN: 1615-6102
    Schlagwort(e): Auxin ; Cell wall ; Coleoptile ; Pectin ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Aiming to elucidate the possible involvement of pectins in auxin-mediated elongation growth the distribution of pectins in cell walls of maize coleoptiles was investigated. Antibodies against defined epitopes of pectin were used: JIM 5 recognizing pectin with a low degree of esterification, JIM 7 recognizing highly esterified pectin and 2F4 recognizing a pectin epitope induced by Ca2+. JIM 5 weakly labeled the outer third of the outer epidermal wall and the center of filled cell corners in the parenchyma. A similar labeling pattern was obtained with 2F4. In contrast, JIM 7 densely labeled the whole outer epidermal wall except the innermost layer, the middle lamellae, and the inner edges of open cell corners in the parenchyma. Enzymatic de-esterification with pectin methylesterase increased the labeling by JIM 5 and 2F4 substantially. A further increase of the labeling density by JIM 5 and 2F4 and an extension of the labeling over the whole outer epidermal wall could be observed after chemical de-esterification with alkali. This indicates that both methyl- and other esters exist in maize outer epidermal walls. Thus, in the growth-controlling outer epidermal wall a clear zonation of pectin fractions was observed: the outermost layer (about one third to one half of wall thickness) contains unesterified pectin epitopes, presumably cross-linked by Ca2+ extract. Tracer experiments with3H-myo-inositol showed rapid accumulation of tracer in all extractable pectin fractions and in a fraction tightly bound to the cell wall. A stimulatory effect of IAA on tracer incorporation could not be detected in any fraction. Summarizing the data a model of the pectin distribution in the cell walls of maize coleoptiles was developed and its implications for the mechanism of auxin-induced wall loosening are discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01280373
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  • 72
    Digitale Medien
    Digitale Medien
    Chromosome endoreduplication in endosperm cells of two maize genotypes and their progenies (1995)
    Springer
    Protoplasma 189 (1995), S. 156-162 
    Details
    ISSN: 1615-6102
    Schlagwort(e): Chromosome endoreduplication ; Endosperm ; Protein accumulation ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Chromosome endoreduplication is a very common process in higher plants but its function and genetic control are still to be clarified. In our experiments we analyzed, by Feulgen cytophotometry, chromosome endoreduplication in endosperm cells of two maize genotypes, IHP and ILP, having high and low protein content in their seed, respectively. Chromosome endoreduplication occurs in both lines within 24 days after pollination, attaining a maximum ploidy level of 384C (7 DNA replication rounds) in IHP and of 192C (6 replication rounds) in ILP. In the mature seed, endosperms of the two lines show different mean ploidy level. In reciprocal crosses between IHP and ILP the f1 endosperms have mean ploidy levels analogous to that of the maternal parent, showing that the difference in ploidy level between the two genotypes is maintained. After selfing of the f1 plants, the difference in ploidy level between the two F2 populations is reduced. In F2 the mean ploidy level is as variable as in f1, indicating the absence of genetic segregation. From our data, it is apparent that both the genetic constitution (cytoplasmic and nuclear) of the maternal parent and the genotype of the individual endosperms influence the ploidy level. An analysis of the protein content in endosperms carried out on the same seed sample as analyzed cytophotometrically showed that the protein content increases, during seed development, parallel to chromosome endoreduplication and varies, in the two lines, in reciprocal crosses and their progeny, according to the same trend as mean ploidy level, suggesting a correlation between the two parameters.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01280169
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  • 73
    Digitale Medien
    Digitale Medien
    Hexacyanoferrate (III) stimulation of elongation in coleoptile segments fromZea mays L. (1995)
    Springer
    Protoplasma 184 (1995), S. 63-71 
    Details
    ISSN: 1615-6102
    Schlagwort(e): Avena sativa ; Elongation growth ; Glycine max ; Hexacyanoferrate III (ferricyanide) ; Indole-3-acetic acid ; Zea mays
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary The influence of exogenous potassium hexacyanoferrate (III) (HCF III) on elongation of maize (Zea mays L.) coleoptile segments was investigated. Addition of HCF III led to a strong stimulation of growth both in the presence and absence of indole-3-acetic acid (IAA). The magnitude of growth stimulation was dependent on the presence of IAA, HCF III concentration, incubation time, and phase growth. The reduced form, potassium hexacyanoferrate (II), was without effect on growth. In the presence of HCF III, elongation was suppressed when coleoptile segments were treated with N,N′-dicyclohexylcarbodiimide, cycloheximide or atebrine (quinacrine). The addition of HCF III stimulated the IAA-induced proton extrusion, and the e−/H+ ratio decreased with incubation time. HCF III also strongly stimulated elongation ofAvena saliva L. coleoptile segments andGlycine max L. hypocotyl segments. These results suggested that a plasma membrane redox system (NADH oxidase type I) may be involved in the regulation of growth through the activity of the plasma membrane-bound ATPase.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01276902
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  • 74
    Digitale Medien
    Digitale Medien
    Iron and copper in plasma membranes of maize (Zea mays L.) roots investigated by proton induced X-ray emission (1995)
    Springer
    Protoplasma 184 (1995), S. 145-150 
    Details
    ISSN: 1615-6102
    Schlagwort(e): Zea mays ; Plasma membrane ; Proton microprobe ; Copper ; Iron ; Zinc
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Plasma membranes of maize (Zea mays L., cv. Sil Anjou 18) roots were isolated by aqueous two-phase partitioning. Multi elemental analysis by proton induced X-ray emission (PIXE) was used for the investigation of elemental composition of plasma membranes. Fe, Cu, and Zn as well as P, S, and Ca were identified. We did not find significant amounts of V, Mn, Se, Mo, or W.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01276912
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  • 75
    Digitale Medien
    Digitale Medien
    Changes in the glutathione level induced by transplasma membrane electron transport in maize (Zea mays L.) (1995)
    Springer
    Protoplasma 184 (1995), S. 238-248 
    Details
    ISSN: 1615-6102
    Schlagwort(e): Glutathione ; Plasma membrane redox acitvity ; Electron transfer ; Zea mays ; Diamide ; Buthionine-D,L-suIfoximine ; Hexacyanoferrate III ; Hexabromoiridate IV
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary We investigated changes of thiols (GSH, GSSG, and cysteine) induced by transplasma membrane electron transport after addition of artificial electron acceptors and the influence of the thiol level on redox activity. GSH, GSSG, and cysteine content of maize (Zea mays L. cv. Golden Bantam) roots and coleoptile segments was determined by high performance liquid chromatography with a fluorescence detector. GSSG increased after treatment with 0.8 mM diamide, an SH-group oxidizer. GSH level of roots increased after treatment with diamide, while GSH levels of coleoptiles decreased. Incubation of roots with the GSH biosynthesis inhibitor buthionine-D,L-sulfoximine for 6 days lowered the glutathione level up to 80%. However, the GSH/GSSG ratio of maize roots remained constant after treatment with both effectors. The GSH/GSSG ratio and the glutathione level were changed by addition of artificial electron acceptors like hexacyanoferrate (III) or hexabromoiridate (IV), which do not permeate the plasma membrane. Hexacyanoferrate (III) reduction was inhibited up to 25% after the cellular glutathione level was lowered by treatment with diamide or buthionine-D,L-sulfoximine. Proton secretion induced by reduction of the electron acceptors was not affected by both modulators. The change in glutathione level is different for roots and coleoptiles. Our data are discussed with regard to the role of GSH in electron donation for a plasma membrane bound electron transport system.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01276927
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  • 76
    Digitale Medien
    Digitale Medien
    A phase II and pharmacokinetic study of 6S-leucovorin plus 5-fluorouracil in patients with colorectal carcinoma (1995)
    Springer
    Investigational new drugs 13 (1995), S. 149-155 
    Details
    ISSN: 1573-0646
    Schlagwort(e): leucovorin ; colorectal cancer ; pharmacokinetics ; chemotherapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Leucovorin (LV) is commonly used as a modulator of 5-fluorouracil (5-FU) cytotoxicity. In patients with colon cancer, the addition of LV to 5-FU improves response rates, and in some trials has improved survival in advanced disease and in the adjuvant setting. Leucovorin is generally administered as a racemic mixture, but the isomers differ substantially in pharmacokinetics and biological activity, with 6S-LV the predominant active component. The current study was undertaken to determine the effect of 6R on the pharmacokinetics of 6S-LV, and to characterize the toxicity and antitumor effect of 5-FU when administered with 6S-LV to patients with advanced colorectal carcinoma. Thirty patients were treated with weekly 5-FU plus high dose 6S-LV. To determine the effects of 6R-LV on the pharmacokinetics of 6S-LV, 20 patients were randomly assigned to receive either 250 mg/m2 6S-LV or 500 mg/m2 6R,S-LV as a 2 hour IV infusion on day −2, and the other preparation on day −1, with pharmacokinetics measured each day. The presence of 6R-LV had no effect on the AUC, Clp, Cmax, or terminal phase t1/2 of 6S-LV. The overall response rate was 40% (C.I. 23–60%). The most frequent toxicities were gastrointestinal. In this small cohort, scheduled and delivered dose intensity was positively associated with response (p=0.05). These results show that there is no pharmacokinetic advantage to the use of 6S-LV rather than 6R,S-LV as a modulator of 5-FU.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00872864
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  • 77
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of Antimony in Patients Treated with Sodium Stibogluconate for Cutaneous Leishmaniasis (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 113-116 
    Details
    ISSN: 1573-904X
    Schlagwort(e): antimony ; sodium stibogluconate ; pentavalent antimonials ; pharmacokinetics ; cutaneous leishmaniasis ; antimony in whole blood ; urinary excretion of antimony ; interpatient variability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The pharmacokinetics of Sb was examined in 29 patients with cutaneous leishmaniasis following the intramuscular administration of a dose of sodium stibogluconate equivalent to 600 mg of Sb. Blood was sampled at different time intervals from each patient and Sb was measured in whole blood by electrothermal atomic absorption spectrophotometry after an appropriate dilution with Triton X-100. The 24-hr urine- was also collected and analyzed similarly. The blood concentration-time data conformed to the one-compartment open model with mean and (SEM) of the apparent first-order rate constants for absorption (ka) and elimination (kd) of 1.71 (0.15) and 0.391 (0.016) hr−1, respectively. The maximum concentration of Sb achieved was 8.77 (0.39) mg/L and the peak time was 1.34 (0.09) hr. The total body clearance (TBC) and the volume of distribution (Vd) were 17.67 (1.38) L/hr and 45.7 (2.6) L, respectively, assuming a complete absorption. The fraction of dose of Sb excreted in the urine was 0.80 (0.07) and the renal clearance was 12.7 (1.16) L/hr. The frequency distribution pattern of the area-under-the-curve (AUC) appears to be bimodal and separates patients into those with low exposure to Sb (AUC = 11.7-29.04 mg.hr/L) (i.e., rapid eliminators) and those with high exposure to Sb (AUC = 31.5-49.1 mg.hr/ L) (i.e., slow eliminators). This may explain the variability observed in the response to treatment of leishmaniasis with sodium stibogluconate.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016251023427
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  • 78
    Digitale Medien
    Digitale Medien
    Assessment of Toxicokinetics and Toxicodynamics Following Intravenous Administration of Etoposide Phosphate in Beagle Dogs (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 117-123 
    Details
    ISSN: 1573-904X
    Schlagwort(e): BMY-40481 ; etoposide phosphate ; etoposide ; pharmacokinetics ; pharmacodynamics ; dogs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The toxicokinetics and toxicodynamics of etoposide phosphate (BMY-40481), a water soluble phosphate ester derivative of etoposide, were investigated in beagle dogs (N = 4) following 5 min i.v. infusion doses equivalent to 57, 114 and 461 mg/m2 of etoposide. The doses were administered in sequence starting with the low dose. There was a 28 day wash-out period between the doses. Serial blood samples were collected over 32 hr and the levels of intact BMY-40481 and etoposide in plasma were measured using validated HPLC assays. Hematology profiles were obtained at pre-dose, and twice a week post-dose for 28 days to correlate systemic exposure to etoposide and hematologic toxicity. Following i.v. administration, plasma concentrations of BMY-40481 declined rapidly. For the 3 doses, mean t1/2 of BMY-40481 ranged from 0.11 - 0.17 hr (6.6-11 min). The mean Cmax and AUC values of BMY-40481 ranged from 1.72 - 40.5 µg/ml and 0.16 - 4.14 hr.µg/ml, respectively. Both systemic clearance and steady state volume of distribution of BMY-40481 decreased significantly at the high dose. In contrast, the mean Cmax and AUC values of etoposide ranged from 5.46 - 39.4 µg/ml and 2.28 - 22.6 hr.µg/ml, respectively. Cmax occurred at the end of infusion (5 min) at all dose levels, indicating that etoposide was rapidly formed from BMY-40481. The apparent systemic clearance (range: 342 - 435 ml/min/m2) and apparent steady state volume of distribution (range: 21.5 - 26.6 1/m2) of etoposide were dose-independent. The AUC of etoposide was significantly correlated with hematologic toxicity, i.e., percent decreases in white blood count (WBC), absolute neutrophil count (ANC) and platelets. The relationship was best described by the sigmoid Emax model for WBC and ANC, and by a simple linear model for platelets. Hemoglobin showed slight decreases which did not correlate with etoposide AUC. In summary, BMY-40481 is rapidly and extensively converted to etoposide; etoposide exhibits linear kinetics; and except for hemoglobin, hematologic toxicity is significantly correlated with etoposide exposure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016203107497
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  • 79
    Digitale Medien
    Digitale Medien
    The Effect of Food on Pharmacokinetics of Zalcitabine in HIV-Positive Patients (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1462-1465 
    Details
    ISSN: 1573-904X
    Schlagwort(e): pharmacokinetics ; food ; interaction ; zalcitabine ; HIV infection
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The purpose of this study was to determine the effect of food on the pharmacokinetics of zalcitabine in HIV-positive patients. Methods. Twenty patients received single oral 1.5 mg doses of zalcitabine with and without a standard breakfast in an open-label, randomized crossover study with at least a one week washout period between treatments. Serial blood and urine samples were collected over 24 hours and assayed for zalcitabine by a modified GC/MS method. Results. Administration with food delayed and prolonged absorption resulting in a decrease of approximately 39% in maximal plasma concentrations compared to dosing under fasting conditions. Comparison of plasma AUC values indicated a small (14%) reduction in bioavailability when given with food. Approximately 59% and 45% of the dose were excreted unchanged in the urine under fasting and fed conditions, respectively. Conclusions. The results of this study show that the administration of zalcitabine with food results in a mild reduction in bioavailability. Although these changes are not expected to be of clinical importance, further studies must be conducted for confirmation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016275118710
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  • 80
    Digitale Medien
    Digitale Medien
    A Novel Oligodeoxynucleotide Inhibitor of Thrombin. II. Pharmacokinetics in the Cynomolgus Monkey (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1943-1947 
    Details
    ISSN: 1573-904X
    Schlagwort(e): GS-522 ; oligodeoxynucleotide ; thrombin ; pharmacokinetics ; monkey
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To determine the pharmacokinetics of GS-522, an oligodeoxynucleotide (GGTTGGTGTGGTTGG) inhibitor of thrombin, after constant infusion and bolus administration in the cynomolgus monkey. Methods. Using a stability indicating HPLC method, the GS-522 plasma concentration versus time data were obtained after constant infusion (0.1, 0.3, 0.5 mg/kg/min) and bolus administration (11.25 and 22.5 mg/kg). Plasma data after bolus administration was fit to a three-compartment model. Results. The half-lives for the α and β phases were 1.4 and 5.4 min, respectively. Steady state GS-522 concentrations were reached within 10 minutes after initiation of constant infusions. Termination of infusions resulted in a rapid elimination of GS-522 with an average elimination half-life equal to 1.5 min. The Vss calculated from both the constant infusion and bolus data approximated the blood volume of the monkey. Substitution of the phosphodiester backbone at the 3′ end of GS-522 with two phosphorothioate linkages did not substantially effect the elimination half-life upon termination of infusion. Conclusions. These data in conjunction with published biodistribution data suggest that oligodeoxynucleotides are rapidly cleared from plasma by tissue uptake and that little efflux back into blood takes place. Additionally, strategies designed to increase oligodeoxynucleotide resistance to exonucleases will not dramatically increase plasma half-lives.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016295907266
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  • 81
    Digitale Medien
    Digitale Medien
    Regional Drug Delivery II: Relationship Between Drug Targeting Index and Pharmacokinetic Parameters for Three Non-Steroidal Anti-Inflammatory Drugs Using the Rat Air Pouch Model of Inflammation (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1987-1996 
    Details
    ISSN: 1573-904X
    Schlagwort(e): drug targeting index ; regional administration ; pharmacokinetics ; rat air pouch model ; inflammation ; non-steroidal anti-inflammatory drugs ; diclofenac ; piroxicam ; S[ + ]ibuprofen ; albumin flux
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To quantify the advantage gained by direct administration to a target site for two non-steroidal anti-inflammatory drugs (NSAIDs) piroxicam and diclofenac in the rat air pouch model of inflammation. To derive a model relating drug targeting index (DTI) to the pharmacokinetic parameters of the target and systemic sites, and to compare predictions with observations. Methods. DTI was calculated based on area under the concentration time curve at target (pouch) and systemic site (venous blood) following administration into and sampling from both sites. A model was derived relating DTI to systemic clearance, target permeability, plasma protein binding and fraction of the targeted dose that is systemically available. Results. Both NSAIDs exhibited linear pharmacokinetics over the dose ranges studies. They differed primarily in total body clearance which was approximately 16 fold greater for diclofenac (213 ml hr−l per 250 g) than piroxicam (13 ml hr−l per 250 g). Observed DTIs (11, 114 and 276 for piroxicam, S[ + ]ibuprofen [studied previously] and diclofenac) were ranked in order of total body clearance but were approximately 7.5 fold lower than predicted (101, 700 and 2214 respectively). Conclusions. The discrepancy was explained by the influx of the plasma binding protein, albumin, into the target site due to increased vascular permeability associated with the inflammatory response. The originally derived equation for DTI, which assumed only unbound drug diffuses across the target site, was modified to take into account the simultaneous flux of bound drug.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016212510900
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  • 82
    Digitale Medien
    Digitale Medien
    Effects of Gender, Pregnancy, and Anesthesia on the Pharmacokinetics of Zidovudine in Rats (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1647-1651 
    Details
    ISSN: 1573-904X
    Schlagwort(e): zidovudine ; gender ; anesthesia ; pregnant ; pharmacokinetics ; rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The effects of gender, pregnancy and anesthesia on the pharmacokinetics of zidovudine (AZT) were studied in rats. Methods. Unanesthetized male (MR), female (FR) and pregnant (day 20, PR) rats received 50 mg/kg AZT via a jugular vein cannula. Female (FRA), pregnant (day 20, PRA) and pregnant (day 20, PRR) rats maintained under ketamine: acepromazine:xylazine anesthesia also received 50 mg/kg AZT. Two fetuses were removed at each sampling time from the PRR group. Plasma samples were collected and analyzed by RIA. Results. With the exception of a lower non-renal clearance in female rats, there were no gender differences in the disposition of AZT. No significant differences were noted in total clearance, non-renal clearance or volume of distribution between pregnant and female rats, however, significant differences in renal clearance values were evident. Anesthesia resulted in decreased total, renal and non-renal clearances in female and pregnant rats. The removal of fetuses during the experiments did not alter the total clearance of AZT in pregnant rats, however, renal clearance and volume of distribution were decreased by cesarian section. Conclusions. The rat appears to be a suitable laboratory animal model for investigating AZT disposition during pregnancy. However, results of pharmacokinetic studies when animals are maintained under anesthesia with ketamine :acepromazine:xylazine must be interpreted with caution.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016293017318
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  • 83
    Digitale Medien
    Digitale Medien
    Design for Cell-Specific Targeting of Proteins Utilizing Sugar-Recognition Mechanism: Effect of Molecular Weight of Proteins on Targeting Efficiency (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 209-214 
    Details
    ISSN: 1573-904X
    Schlagwort(e): protein targeting ; sugar recognition ; pharmacokinetics ; molecular weight ; liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Hepatic targeting of proteins utilizing the sugar-recognition mechanism was investigated in mice after intravenous injection. Five proteins with different molecular weights, i.e., bovine γ-globulins (IgG), bovine serum albumin (BSA), recombinant human superoxide dismutase (SOD), soybean trypsin inhibitor (STI), and chicken egg white lysozyme (LZM), were modified with 2-imino-2-methoxyethyl 1-thiogalactoside to obtain galactosylated proteins (Gal-IgG, Gal-BSA, Gal-SOD, Gal-STI, and Gal-LZM). The numbers of galactose residues were 38, 20, 11, 6, and 5 for Gal-IgG, Gal-BSA, Gal-SOD, Gal-STI, and Gal-LZM, respectively. All galactosylated proteins were dose-dependently taken up by the liver and the relative amount accumulated in the liver was decreased with an increase of the administered dose. At low doses (0.05 and 0.1 mg/kg), Gal-IgG, Gal-BSA, and Gal-SOD could be taken up by the liver up to more than 70–80% of dose within 10 min after intravenous injection, but the maximum amounts accumulated in the liver were approximately 40 and 30% of the dose for Gal-STI and Gal-LZM, respectively. Pharmacokinetic analysis revealed that the hepatic uptake clearance (CLliver) was quite different around the molecular weight of 32 kDa and correlated with the amount delivered to the liver; Gal-IgG, Gal-BSA, and Gal-SOD has a large CLliver that is close to the hepatic plasma flow rate (85 ml/hr), whereas those of Gal-STI and Gal-LZM were approximately 10 ml/hr at low doses. As for the total amount accumulated in the liver, high glomerular filtration rate of Gal-STI and Gal-LZM was also shown to cause insufficient delivery to the liver apart from being caused by their low CLliver.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016222808484
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  • 84
    Digitale Medien
    Digitale Medien
    Evaluation of Intestinal Absorption into the Portal System in Enterohepatic Circulation by Measuring the Difference in Portal–Venous Blood Concentrations of Diclofenac (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 880-883 
    Details
    ISSN: 1573-904X
    Schlagwort(e): portal–venous blood concentration difference ; enterohepatic circulation ; diclofenac ; portal system ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. We evaluated the first-pass effects in vivo by the intestine and liver during enterohepatic circulation (EHC) by simultaneously measuring the portal and venous plasma concentrations of the rat. Methods. The venous and upper portal blood vessels were cannulated through the jugular and the pyloric veins, respectively, to obtain simultaneously blood samples from both sites. After diclofenac was injected as a bolus through the jugular vein, the concentrations of diclofenac in the portal and jugular veins were measured at time intervals. The absorption rate from the intestinal tract into the portal system was determined using the portal–venous difference in plasma concentrations of diclofenac, considering 40% partitioning of diclofenac into erythrocytes. Results. After one hour, the plasma concentration in the portal vein was always higher than that in the jugular vein in awakening rats with intact EHC (portal–venous blood concentration difference). No portal–venous difference was observed in awakening rats with bile-duct cannulation. Therefore, it was concluded that this portal–venous concentration difference was not due to the hepatic clearance but to diclofenac reabsorption from the intestinal tract. Conclusions. Appropriately 40% of the dose of diclofenac was reabsorbed over 8 hours from the intestinal tract into the portal system. By comparing the reabsorbed amounts in the portal system and in the systemic circulation, the hepatic extraction ratio in vivo (FH) of diclofenac was estimated to be 63%.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016217221977
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  • 85
    Digitale Medien
    Digitale Medien
    Effect of Corticosteroid Binding Globulin on the Pharmacokinetics of Prednisolone in Rats (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 902-904 
    Details
    ISSN: 1573-904X
    Schlagwort(e): corticosteroid binding globulin ; transcortin ; pharmacokinetics ; free hormone hypothesis ; prednisolone ; methylprednisolone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The effect of exogenous corticosteroid binding globulin (CBG) on the pharmacokinetics of intravenous prednisolone was determined in rats to test the “free hormone hypothesis.” Methods. A dose of CBG to yield 95% binding with 1000 ng/ml of prednisolone in vitro in rat plasma or saline was administered before dosing 2 mg/kg of prednisolone hemisuccinate or methylprednisolone intravenously. Drug concentrations in plasma samples were assayed by HPLC. Results. Single administration of CBG decreased apparent prednisolone clearance by 56% (155 to 66 ml/min/kg) and reduced apparent Vss by 35% (4.1 to 2.7 L/kg) (p〈0.001). Methylprednisolone pharmacokinetics, studied as a negative control because the drug does not bind to CBG, did not change. Conclusions. The corticosteroid bound to CBG does not appear to be available for removal by clearance organs.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016225423795
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  • 86
    Digitale Medien
    Digitale Medien
    Metabolism of Dynorphin A 1-13 in Human Blood and Plasma (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1165-1170 
    Details
    ISSN: 1573-904X
    Schlagwort(e): dynorphin Al-13 ; opioid peptides ; metabolism ; pharmacokinetics ; HPLC
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. A detailed investigation of the metabolic routes and rates of Dyn A1-13 in human blood and plasma was performed. Methods. Human plasma was incubated at 37°C with dynorphin A 1-13 (Dyn Al-13, 15-20 µM). The generated dynorphin fragments were separated by a new ion-pair chromatographic method and identified by matrix assisted laser desorption mass spectroscopy. The kinetic behavior of parent compound and metabolites was evaluated in the absence and presence of enzyme inhibitors. Results. The major plasma metabolites of Dyn Al-13 were Dyn A1-12, A2-12, A4-12 and A4-8. Further metabolites were Dyn A2-13, A3-13, A3-12, A5-12, A6-12, A7-12, Al-10, A2-10, A2-8 and A3-8. At 37°C, Dyn Al-13 had a half-life of less than one minute in plasma and blood. Plasma half-lives of major metabolites ranged between 0.5 and 4 min. Inter-and intra-individual differences in healthy volunteers were 30% (c.v.). Dyn Al-13 is mainly metabolized by carboxypeptidases to Dyn Al-12 (80%) and by aminopeptidases to Dyn A2-13 (15%). Dyn A1-12 and Dyn A2-13 are predominantly converted into Dyn A2-12 (67% of Dyn Al-13). Subsequent metabolic steps yield Dyn A3-12 (16%), Dyn A4-12 (37%) and Dyn A4-8 (33%). Aminopeptidases generate Dyn A2-12, A3-12, A4-12, A5-12. ACE metabolizes Dyn Al-12 (19%), A2-12 (33%), A3-12 (34%) and A4-12 (46%). Bestatin-sensitive endopeptidases (possibly endopeptidase 24.11) metabolize 30% of Dyn A2-12. Dyn A4-8 is formed via Dyn A4-12 (23% of Dyn A4-12) and Dyn A2-10 (37% of Dyn A2-10). Conclusions. The combination of enzyme inhibition experiments and noncompartmental kinetic analysis proved to be a powerful tool for the detailed evaluation of the metabolic fate of Dyn Al-13 in human blood and plasma.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016211910107
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  • 87
    Digitale Medien
    Digitale Medien
    Pharmacokinetic Studies of Methotrexate in Plasma and Synovial Fluid Following IV Bolus and Topical Routes of Administration in Dogs (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1474-1477 
    Details
    ISSN: 1573-904X
    Schlagwort(e): methotrexate ; pharmacokinetics ; synovial fluid ; poloxamer gel ; muscle tissue
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The pharmacokinetic properties of methotrexate (MTX) in the plasma and synovial fluid (SF) after bolus IV and topical administration were studied in dogs to assess the feasibility of topical delivery of MTX for the treatment of rheumatoid arthritis. Methods. A MTX gel in Poloxamer 407 containing an absorption enhancer was formulated and topically applied on the elbow and stifle joints of dogs. SF was collected by inserting a needle with syringe into the joint space. Drug concentrations in the plasma, SF and muscle tissues were determined using a HPLC method with fluorimetric detection. Results. Peak MTX concentrations in SF occurrred at 38 ± 5 min following bolus IV dose, indicating the presence of a substantial diffusion barrier between the plasma and SF. The plasma/SF concentration ratios of 1.16 ± 0.25 were maintained after the attainment of distribution equilibrium between the two compartments. The t1/2 values in the plasma (11.2 ± 1.2 hr) and SF (12.7 ± 3.7 hr) were similar during the elimination phase, while the MRT in SF (3.24 ± 0.21 hr) was longer than that in plasma (2.56 ± 0.20 hr), probably due to the slow distribution of MTX to SF. After topical dose, MTX concentrations in plasma reached the steady state at ~4 hr, lasting for ~20 hr.The bioavailability of MTX from the gel was 11.8 ± 3.3% of the applied dose, but muscle tissues beneath the gel application site had significantly higher levels of MTX than untreated muscle tissues. There was no statistical difference in SF concentrations of MTX between drug treated and untreated joints 24 hr after topical dose. Conclusions. Topical delivery of MTX in a hydrophilic gel achieved a sustained C/t profile in plasma and higher drug levels in muscle tissues underneath the dosing site, implicating the potential therapeutic value of the topical formulation. Methods. A MTX gel in Poloxamer 407 containing an absorption enhancer was formulated and topically applied on the elbow and stifle joints of dogs. SF was collected by inserting a needle with syringe into the joint space. Drug concentrations in the plasma, SF and muscle tissues were determined using a HPLC method with fluorimetric detection. Results. Peak MTX concentrations in SF occurrred at 38 ± 5 min following bolus IV dose, indicating the presence of a substantial diffusion barrier between the plasma and SF. The plasma/SF concentration ratios of 1.16 ± 0.25 were maintained after the attainment of distribution equilibrium between the two compartments. The t1/2 values in the plasma (11.2 ± 1.2 hr) and SF (12.7 ± 3.7 hr) were similar during the elimination phase, while the MRT in SF (3.24 ± 0.21 hr) was longer than that in plasma (2.56 ± 0.20 hr), probably due to the slow distribution of MTX to SF. After topical dose, MTX concentrations in plasma reached the steady state at ~4 hr, lasting for ~20 hr.The bioavailability of MTX from the gel was 11.8 ± 3.3% of the applied dose, but muscle tissues beneath the gel application site had significantly higher levels of MTX than untreated muscle tissues. There was no statistical difference in SF concentrations of MTX between drug treated and untreated joints 24 hr after topical dose. Conclusions. Topical delivery of MTX in a hydrophilic gel achieved a sustained C/t profile in plasma and higher drug levels in muscle tissues underneath the dosing site, implicating the potential therapeutic value of the topical formulation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016231303689
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  • 88
    Digitale Medien
    Digitale Medien
    Intra- and Inter-Subject Variabilities of CGP 33101 after Replicate Single Oral Doses of Two 200-mg Tablets and 400-mg Suspension (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1878-1882 
    Details
    ISSN: 1573-904X
    Schlagwort(e): CGP 33101, intra-subject variability ; inter-subject variability ; pharmacokinetics ; healthy subjects ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The purpose of this study was to use a replicate designed trial to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters of CGP 33101 after oral administration of tablets relative to that of powder suspended in water, and to determine the relative proportion of the intra-subject variance to the overall variability. Methods. Sixteen healthy subjects were randomly assigned to four groups to receive tablets and suspension twice in four different treatment sequences. The plasma concentration-time profile of CGP 33101 was characterized in terms of Cmax, Tmax, and AUC. Bioavailability of tablets relative to suspension and intra- and inter-subject variability were assessed by statistical analysis. Results and Conclusions. The overall variabilities in absorption kinetics of CGP 33101 in healthy subjects were small with CV's of the population mean values for AUC and Cmax less than 26% for both tablets and suspension. Contribution of intra-subject variability to the overall variability was also small (~20%). Both the overall and intra-subject variabilities of AUC and Cmax after suspension were larger than after the tablets. However, the differences in variability between tablets and suspension were not statistically significant (p 〉 0.05). The tablet formulation was bioequivalent to suspension in terms of rate and extent of absorption based on 90% conventional confidence intervals (for AUC and Cmax) and Wilcoxon rank-sum test (for Tmax).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016275402723
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  • 89
    Digitale Medien
    Digitale Medien
    Effect of Probenecid on the Enantioselective Pharmacokinetics of Oxprenolol and Its Glucuronides in the Rabbit (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1964-1967 
    Details
    ISSN: 1573-904X
    Schlagwort(e): enantioselectivity ; pharmacokinetics ; oxprenolol ; oxprenolol glucuronides ; probenecid ; active renal secretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To study the effect of probenecid on the stereoselective pharmacokinetics of oxprenolol and its glucuronides in the rabbit. Methods. An oral dose of 50 mg/kg racemic oxprenolol was given to nine rabbits twice, in random sequence with and without the concurrent administration of probenecid. Oxprenolol enantiomers were determined in plasma and urine by an enantioselective HPLC method. Oxprenolol glucuronides were measured in plasma and urine after enzymatic hydrolysis. Results. The disposition of the oxprenolol enantiomers in rabbits is stereoselective, mainly due to a difference in metabolism. Renal excretion is only a minor elimination route for unchanged oxprenolol, and the renal clearances of the enantiomers are similar. Pre-treatment with probenecid did not affect the plasma concentrations of the oxprenolol enantiomers, but there was a slight decrease in their urinary excretion. The plasma concentrations of the oxprenolol glucuronides are much higher than those of the parent enantiomers, and those of (S)-glucuronide are about twice those of its antipode. About 10% of the oxprenolol dose is excreted in the urine as glucuronides. The renal clearances of both glucuronides are similar, and markedly higher than the creatinine clearance. After probenecid, the mean glucuronide plasma levels were markedly higher, with for both glucuronides a more than twofold increase in mean AUC. Probenecid decreased the renal clearance of both glucuronides to about 30%. Moreover, it decreased slightly the formation clearance of (S)-glucuronide, while the formation clearance of (R)-glucuronide was not significantly influenced. Conclusions. Our results show that in the rabbit, both oxprenolol glucuronide diastereomers are actively secreted by the kidney, and that this process is inhibited by probenecid.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016204309083
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  • 90
    Digitale Medien
    Digitale Medien
    Microdialysis Sampling to Determine the Pharmacokinetics of Unbound SDZ ICM 567 in Blood and Brain in Awake, Freely-Moving Rats (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 291-294 
    Details
    ISSN: 1573-904X
    Schlagwort(e): brain microdialysis ; blood microdialysis ; pharmacokinetics ; free drug concentration ; SDZ ICM 567
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The free concentrations of the serotoninergic 5-HT3 antagonist SDZ ICM 567 in blood and in the central nervous system were examined in awake, freely-moving rats using blood and brain microdialysis coupled to liquid chromatography. Microdialysis probes were implanted in the jugular vein and in the frontal cortex and dialysis samples were simultaneously collected from both sites. Pharmacokinetic parameters were calculated after a 10 mg/kg intravenous dose of [14C]SDZ ICM 567. The elimination half lives measured in whole blood, brain and blood microdialysates were similar (≃1.7 h). The AUC0–5h corresponding to the unbound drug was 462 ± 142 ng · ml−1 · h in blood dialysate, not significantly different from the AUC corresponding to the free concentration in whole blood, i.e. 586 ± 63 ng · ml−1 h. The free fraction in blood obtained in vitro by equilibrium dialysis (21%) or by microdialysis (19%) was not statistically different from that obtained in vivo (17%) in microdialysis experiments. The unbound concentrations (AUC0–5h) of SDZ ICM 567 in the brain cortex were 86 ± 24 ng · ml−l - h, lower than those expected from unbound blood concentrations, suggesting an active transport out of the central nervous system. Finally, microdialysis sampling allowed the determination of pharmacokinetic parameters of SDZ ICM 567 in blood and brain as well as the estimation of the free fraction of drug in blood.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016247413935
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  • 91
    Digitale Medien
    Digitale Medien
    The Influence of Regional Deposition on the Pharmacokinetics of Pulmonary-Delivered Human Growth Hormone in Rabbits (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 356-359 
    Details
    ISSN: 1573-904X
    Schlagwort(e): growth hormone ; pulmonary ; pharmacokinetics ; gamma scintigraphy ; drug delivery ; rabbit
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The pulmonary deposition and pharmacokinetics of human growth hormone (hGH), administered by aerosol and instillate, in formulations containing 99mTc-DTPA (for gamma scintigraphic imaging) have been studied in five male New Zealand White rabbits. Gamma scintigraphy indicated that the peripheral:central deposition tended to be greater for aerosol (1.54) than for instillate (0.8). Two gamma scintigraphic methods were used to quantify dose deposited by aerosol, which permitted bioavailabilities to be determined. The bioavailable fraction for aerosolized hGH (45%) was greater than for instilled hGH (16%). This was attributed to the differential effects of mucociliary clearance. Absorption rate limited pharmacokinetics prevailed for both hGH formulations with post-peak half-lives approximately 10-fold greater than the intravenous elimination half-life of 40 min. Apparent absorption rate constants resulting from instillation and aerosolization were equivalent (0.0012 min−1and 0.0020 min−1respectively), however lung-to-blood transfer rate constants for aerosol delivery (0.00071 min −l) were greater than for instillation (0.00018 min−1).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016292232513
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  • 92
    Digitale Medien
    Digitale Medien
    Pharmacokinetic/Pharmacodynamic Evaluation of Deflazacort in Comparison to Methylprednisolone and Prednisolone (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1096-1100 
    Details
    ISSN: 1573-904X
    Schlagwort(e): pharmacokinetics ; pharmacodynamics ; corticosteroids ; metabolites ; prodrug
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The pharmacokinetics and pharmacodynamics of deflazacort after oral administration (30 mg) to healthy volunteers were determined and compared with those of 20 mg of methylprednisolone and 25 mg of prednisolone. Methods. Methylprednisolone, prednisolone and the active metabolite of deflazacort, 21-desacetyldeflazacort, were measured in plasma using HPLC. For the assessment of pharmacodynamics, differential white blood cell counts were obtained over 24 hours. An integrated pharmacokinetic-pharmacodynamic (PK-PD) model was applied to link corticosteroid concentrations to the effect on lymphocytes and granulocytes. Results. Deflazacort is an inactive prodrug which is converted rapidly to the active metabolite 21-desacetyldeflazacort. Maximum concentrations of 21-desacetyldeflazacort averaged 116 ng/ml and were observed after 1.3 h. The average area under the curve was 280 ng/ml · h, and the terminal half-life was 1.3 h. 21-Desacetyldeflazacort was cleared significantly faster than both methylprednisolone and prednisolone. The PK-PD-model was suitable to describe time course and magnitude of the observed effects. The results were consistent with reported values for glucocorticoid receptor binding affinities for the investigated compounds. Conclusions. Due to the short pharmacokinetic half-life of its active metabolite, pharmacodynamic effects of deflazacort are of shorter duration than those of methylprednisolone and prednisolone. The PK-PD model allows good prediction of pharmacodynamic effects based on pharmacokinetic and receptor binding data.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016287104656
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  • 93
    Digitale Medien
    Digitale Medien
    Liposomal Formulations of Cyclosporin A: Influence of Lipid Type and Dose on Pharmacokinetics (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1189-1198 
    Details
    ISSN: 1573-904X
    Schlagwort(e): cyclosporins ; liposomal membranes ; lipid dose ; rat ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. Liposomal formulations of Cyclosporin A (CyA)3 have been described in more than 30 publications to substitute Cremophor EL (CrEL), a triricinoleate ester of ethoxylated glycerol, as drug carrier. However, conflicting reports did not allow to draw consistent conclusions about the influence of liposomes on CyA pharmacokinetics (PK) and pharmacodynamics. Methods. A series of liposomal CyA-formulations with varying liposome composition and lipid dose but constant CyA dose was compared in rats. Data were analysed with a PK-model taking into account the varying volume of distribution with the varying lipid concentration in blood. Results. Surface properties and lipid type of liposomes are not important PK predictors of liposomal CyA, at least for small dosages of liposomes. Rather, the absolute lipid amount and the lipophilicity of cyclosporins are critical factors influencing the PK of liposomal CyA. The higher the concentration of lipid in blood and the greater the lipophilicity of cyclosporin is, the higher are the concentrations of CyA in blood. Conclusions. These relations may explain the inconsistent literature results. Together with earlier observations from our group the above findings indicate, that CyA is not caged in the liposomal membranes. Reports in literature, which claim lower clearance and a lower volume of distribution of CyA in obese rats compared to lean rats, support our assumption about the involved mechanisms. A semi-quantitative model of CyA distribution is presented, which points to the variable free fraction of CyA in plasma as the crucial factor for all previously reported phenomena in liposomal CyA formulations.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016220211925
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  • 94
    Digitale Medien
    Digitale Medien
    Disease levels in winter wheat, rye and triticale grown on soil artificially inoculated withCephalosporium gramineum (1995)
    Springer
    European journal of plant pathology 101 (1995), S. 701-704 
    Details
    ISSN: 1573-8469
    Schlagwort(e): Cephalosporium gramineum ; Cephalosporium stripe ; rye ; susceptibility ; triticale ; wheat ; winter cereals
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Field experiments with winter cereals grown on soil inoculated withC. gramineum showed that wheat and rye cultivars possess some resistance to the pathogen, while the triticale cultivars were the most susceptible. Higher tolerance of the tested wheat cultivars was connected mainly with slow development of disease symptoms; rye cultivars had, on average, lower percentages of plants infected byC. gramineum. The greatest variation in susceptibility toC. gramineum occurred among the selected cultivars of triticale.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01874875
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  • 95
    Digitale Medien
    Digitale Medien
    Development of apothecia ofTapesia yallundae in contrasting populations selected by fungicides (1995)
    Springer
    European journal of plant pathology 101 (1995), S. 695-699 
    Details
    ISSN: 1573-8469
    Schlagwort(e): Pseudocercosporella herpotrichoides ; eyespot ; wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Apothecia of the eyespot fungus,Tapesia yallundae, were found on 0–18% of straws in plots of wheat stubble in February–March 1994. The fungicides carbendazim, prochloraz or carbendazim plus prochloraz had been applied repeatedly to the same plots in each of the previous 9 years in which successive wheat crops had been grown. The factors most strongly correlated with the incidence of apothecia were the incidence and severity of eyespot in the preceding wheat crop and the frequency of carbendazim-resistant W-type fungus in populations recovered from that wheat crop. Plots treated with carbendazim, which had previously had more disease and more resistance to carbendazim in the pathogen population relative to untreated plots, therefore yielded most apothecia. Plots treated with prochloraz, which had selected for predominantly R-type fungus and decreased eyespot, yielded few apothecia. Single-ascospore isolates were all of the W-type and were more frequently carbendazim-sensitive than expected, except those from plots treated only with carbendazim. None showed decreased sensitivity to prochloraz. The implications of applying fungicides regularly for controlling eyespot on the capability of the eyespot fungus for genetic variation through sexual reproduction are discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01874874
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  • 96
    Digitale Medien
    Digitale Medien
    Third-generation model for corticosteroid pharmacodynamics: Roles of glucocorticoid receptor mRNA and tyrosine aminotransferase mRNA in rat liver (1995)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 23 (1995), S. 163-181 
    Details
    ISSN: 1573-8744
    Schlagwort(e): methylprednisolone ; pharmacokinetics ; pharmacodynamics ; glucocorticoid receptor ; tyrosine aminotransferase ; Northern hybridization ; mRNA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A third-generation pharmacokinetic/pharmacodynamic model was proposed for receptor/genemediated corticosteroid effects. The roles of the messenger RNA (mRNA) for the glucocorticoid receptor (GR) in hepatic GR down-regulation and the mRNA for hepatic tyrosine aminotransferase (TAT) induction by methylprednisolone (MPL) were examined. Male adrenalectomized Wistar rats received 50 mg/kg MPL iv. Blood and liver samples were collected at various time points for a period of 18 hr. Plasma concentrations of MPL, free hepatic cytosolic GR densities, GR mRNA, TAT mRNA, and TAT activities in liver were determined. Plasma MPL profile was biexponential with a terminal t1/2 of 0.57 hr. Free hepatic GR density rapidly disappeared from cytoplasm after the MPL dose and then slowly returned to about 60% of starting level after 16 hr. Meanwhile, GR mRNA level fell to 45% of baseline within 2 hr postdosing, and remained at that level for at least 18 hr. The GR down-regulation of GR mRNA and protein turnover rate were modeled. The TAT mRNA began to increase at about 2 hr, reached a maximum at about 5 hr, and declined to baseline by 14 hr. TAT induction followed a similar pattern, except the induction was delayed about 0.5 hr. Pharmacodynamic parameters were obtained by fitting seven differential equations in a piecewise fashion. The cascade of corticosteroid steps were modeled by a series of inductions for steroid-receptor-DNA complex, two intermediate transit compartments, TAT mRNA, and TAT activity. Results indicate that GR mRNA and TAT mRNA are major controlling factors for the receptor/gene-mediated effects of corticosteroids.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02354270
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  • 97
    Digitale Medien
    Digitale Medien
    Bayesian design criteria: Computation, comparison, and application to a pharmacokinetic and a pharmacodynamic model (1995)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 23 (1995), S. 101-125 
    Details
    ISSN: 1573-8744
    Schlagwort(e): Bayesian designs ; Bayesian estimation ; prior distribution ; pharmacokinetics ; pharmacodynamics ; E max model ; nonlinear models
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract In this paper 3 criteria to design experiments for Bayesian estimation of the parameters of nonlinear models with respect to their parameters, when a prior distribution is available, are presented: the determinant of the Bayesian information matrix, the determinant of the preposterior covariance matrix, and the expected information provided by an experiment. A procedure to simplify the computation of these criteria is proposed in the case of continuous prior distributions and is compared with the criterion obtained from a linearization of the model about the mean of the prior distribution for the parameters. This procedure is applied to two models commonly encountered in the area of pharmacokinetics and pharmacodynamics: the one-compartment open model with bolus intravenous single-dose injection and theE max model. They both involve two parameters. Additive as well as multiplicative gaussian measurement errors are considered with normal prior distributions. Various combinations of the variances of the prior distribution and of the measurement error are studied. Our attention is restricted to designs with limited numbers of measurements (1 or 2 measurements). This situation often occurs in practice when Bayesian estimation is performed. The optimal Bayesian designs that result vary with the variances of the parameter distribution and with the measurement error. The two-point optimal designs sometimes differ from the D-optimal designs for the mean of the prior distribution and may consist of replicating measurements. For the studied cases, the determinant of the Bayesian information matrix and its linearized form lead to the same optimal designs. In some cases, the pre-posterior covariance matrix can be far from its lower bound, namely, the inverse of the Bayesian information matrix, especially for theE max model and a multiplicative measurement error. The expected information provided by the experiment and the determinant of the pre-posterior covariance matrix generally lead to the same designs except for theE max model and the multiplicative measurement error. Results show that these criteria can be easily computed and that they could be incorporated in modules for designing experiments.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02353788
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  • 98
    Digitale Medien
    Digitale Medien
    A semicompartmental modeling approach for pharmacodynamic data assessment (1995)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 23 (1995), S. 307-322 
    Details
    ISSN: 1573-8744
    Schlagwort(e): effect-site link model ; semicompartmental model ; model misspecification ; pharmacokinetics ; pharmacodynamics ; nonlinear regression
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A new method is proposed for modeling the temporal aspects of the pharmacodynamic-pharmacokinetic relationship of drugs. A semicompartmental solution to the effect-site link model of Sheiner et al. (1) formed the basis for this new approach. This semicompartmental solution does not require the specification of a compartmental model for the pharmacokinetic response and may offer an advantage when model misspecification is present in using standard compartmental models. A Monte Carlo simulation study was conducted to evaluate the performance of the semicompartmental modeling approach. This method is easily implemented in standard nonlinear regression packages.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02354287
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  • 99
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and Anticonvulsant Effect of a New Hypnotic, CL 284,846, in Rats (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1592-1597 
    Details
    ISSN: 1573-904X
    Schlagwort(e): anticonvulsant ; CL 284,846 ; CL 284,859 ; pentylenetetrazol ; pharmacokinetics ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. CL 284,846 (CL846) is an investigational non-benzodiazepine agent with hypnotic, anxiolytic, myorelaxant and anticonvulsant properties. This study assessed the pharmacokinetics and anticonvulsant action of CL846 in female Sprague-Dawley rats. Methods. CL846 pharmacokinetics were examined after either an iv bolus dose (2.5 mg/kg) or a 6-hr infusion (0.4 mg/kg/hr). CL846 pharmacodynamics were evaluated with a pentylenetetrazol (PTZ) infusion 5 min after a CL846 in bolus dose (0 to 10 mg/kg). CL846 and the derived metabolite CL 284,859 (CL859) concentrations in serum and brain tissue were determined by HPLC with fluorescence detection. Results. Both the steady-state volume of distribution (1636 ± 162 and 1804 ± 293 ml/kg, after bolus and infusion administration, respectively) and systemic clearance (19.1 ± 7.1 and 22.2 ± 4.3 ml/min/kg for bolus and infusion administration, respectively) were high. No differences in pharmacokinetic parameters were noted between the two modes of administration. The relationship between anticonvulsant effect and brain/serum concentrations was well described by an Emax model. CL846 was as effective as triazolam in antagonizing PTZ-induced seizures. Conclusions. Under the conditions of the present study, CL846 pharmacokinetics were linear and stationary. Further evaluation of the anticonvulsant properties of CL846 is warranted, including the potential development of tolerance, which is well known for benzodiazepines.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016224629614
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  • 100
    Digitale Medien
    Digitale Medien
    MicroPharm-K, a Microcomputer Interactive Program for the Analysis and Simulation of Pharmacokinetic Processes (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1225-1230 
    Details
    ISSN: 1573-904X
    Schlagwort(e): pharmacokinetics ; nonlinear minimisation ; computer program ; software ; estimation ; simulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The microcomputer program, MicroPharm-K (MP-K) was developed for pharmacokinetic modeling, including analysis of experimental data and estimation of relevant parameters, and simulation. The intention was to provide a user-friendly, interactive, event-driven program for PC computers. Methods. The data are ascribed to a predefined model from a library including various routes of administration, oral or intra-venous, bolus or infusion, and various compartmental interpretations, 1 to 3. Single and multiple administrations are supported. The program provides initial estimates of the parameters in most cases, and the parameters are then fitted to the model by non linear model fitting using either the Simplex, Evol, Gauss-Newton, Levenberg-Marquardt or Fletcher-Powell algorithms. The non linear model fitting is based on the maximum likelihood method, and the criterion to minimize is either the weighted least squares (Chi2 criterion) or the extended least squares. Graphical representations of non-fitted or curve-fitted data are immediately available (including log-scale representation), as well as pharmacokinetic typical parameters such as area under the curve, clearance, volumes, time-rate constants, transfer rate constants, etc. Results. Simulated and experimental data were analysed and the results were similar to those obtained by other programs. Conclusions. This non linear fitting program has been proved in our laboratory to be a very effective package for pharmacokinetic studies, including estimation and simulation. Because it is easy-to-use and runs on basic computers, the program could also be used for educational purposes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1016280430580
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