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  • pharmacokinetics  (800)
  • wheat  (568)
  • Springer  (1,368)
  • American Meteorological Society
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Risk analysis 19 (1999), S. 711-726 
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
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  • 2
    ISSN: 1539-6924
    Keywords: MeHg ; pharmacokinetics ; PBPK model ; variability ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract An analysis of the uncertainty in guidelines for the ingestion of methylmercury (MeHg) due to human pharmacokinetic variability was conducted using a physiologically based pharmacokinetic (PBPK) model that describes MeHg kinetics in the pregnant human and fetus. Two alternative derivations of an ingestion guideline for MeHg were considered: the U.S. Environmental Protection Agency reference dose (RfD) of 0.1 μg/kg/day derived from studies of an Iraqi grain poisoning episode, and the Agency for Toxic Substances and Disease Registry chronic oral minimal risk level (MRL) of 0.5 μg/kg/day based on studies of a fish-eating population in the Seychelles Islands. Calculation of an ingestion guideline for MeHg from either of these epidemiological studies requires calculation of a dose conversion factor (DCF) relating a hair mercury concentration to a chronic MeHg ingestion rate. To evaluate the uncertainty in this DCF across the population of U.S. women of child-bearing age, Monte Carlo analyses were performed in which distributions for each of the parameters in the PBPK model were randomly sampled 1000 times. The 1st and 5th percentiles of the resulting distribution of DCFs were a factor of 1.8 and 1.5 below the median, respectively. This estimate of variability is consistent with, but somewhat less than, previous analyses performed with empirical, one-compartment pharmacokinetic models. The use of a consistent factor in both guidelines of 1.5 for pharmacokinetic variability in the DCF, and keeping all other aspects of the derivations unchanged, would result in an RfD of 0.2 μg/kg/day and an MRL of 0.3 μg/kg/day.
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  • 3
    Electronic Resource
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    Springer
    Entomologia experimentalis et applicata 74 (1995), S. 115-119 
    ISSN: 1570-7458
    Keywords: wheat ; aphids ; hydroxamic acids ; DIMBOA ; DIMBOA-glucoside ; EPG ; electrical penetration graph ; feeding deterrents ; antixenosis ; plant resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: 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.
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  • 4
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    Entomologia experimentalis et applicata 74 (1995), S. 283-294 
    ISSN: 1570-7458
    Keywords: hypersensitivity ; Hessian fly ; plant resistance ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: 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.
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  • 5
    Electronic Resource
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    Entomologia experimentalis et applicata 68 (1993), S. 219-229 
    ISSN: 1570-7458
    Keywords: Hymenoptera ; Aphidiidae ; Homoptera ; Aphididae ; Schizaphis graminum ; wheat ; tritrophic interactions ; learning ; host-habitat location
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The effect of experience on the responsiveness of the aphidiid parasitoidLysiphlebus testaceipes (Cresson) (Hymenoptera: Aphidiidae) to host-associated cues was investigated using a wind-tunnel bioassay. Naive females were able to discriminate between uninfested wheat (Triticum aestivum L.) and wheat infested withSchizaphis gramimum (Rondani) (Homoptera: Aphididae), but oviposition experience significantly increased the parasitoid's propensity to respond to aphid-infested plants with upwind, targeted flight. The behavioural change associated with such experience was acquired rapidly (within five minutes) and persisted for at least 24 h. The parasitoid could be successfully conditioned to associate a novel odour with the presence of hosts, suggesting that the increase in response to aphid-infested plants which occurs as a result of experience is probably due to associative learning of olfactory cues from the plant-aphid complex.
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  • 6
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    Entomologia experimentalis et applicata 93 (1999), S. 227-230 
    ISSN: 1570-7458
    Keywords: Rhopalosiphum padi ; cereal aphids ; wheat ; induced responses ; feeding site
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 7
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    Entomologia experimentalis et applicata 92 (1999), S. 157-164 
    ISSN: 1570-7458
    Keywords: plant resistance ; antibiosis ; tolerance ; antixenosis ; Russian wheat aphid ; wheat ; Homoptera ; Aphididae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The Russian wheat aphid, Diuraphis noxia (Mordvilko), is one of the most important aphid pests of wheat, Triticum aestivum L., worldwide. Among the various pest management options, plant resistance is an economical management tactic to control D. noxia in cereal crops such as wheat. Researchers have identified D. noxia resistant germplasm and it has been incorporated into wheat. This study compared D. noxia resistance between the ‘Betta’ wheat isolines Betta-Dn1, Betta-Dn2, and Betta-Dn5 and their corresponding donor gene plant introduction (PI) lines PI 137739 (Dn1), PI 262660 (Dn2), and PI 294994 (Dn5). Although the Betta isolines and PI lines showed D. noxia resistance when compared with Betta wheat, the degree of resistance in the isolines to D. noxia was different from their corresponding PI donors. Aphid number, aphid fecundity, and biomass per aphid were not different between Betta-Dn1 and PI 137739 or Betta-Dn2 and PI 262660; however, the same parameters were significantly lower on PI 294994 compared with Betta-Dn5. This indicated that aphid resistance in PI 137739 and PI 262660 was probably governed by a single dominant gene, while the resistance in PI 294994 was controlled by more than one gene. Additionally, plant biomass reduction was aphid density dependent, which suggested that use of appropriate aphid infestation level is important when using plant biomass reduction as an indicator of resistance. Plant resistance categorization showed that there was no detectable difference in antixenosis among the seven lines evaluated. However, the higher aphid fecundity observed on PI 262660 compared with PI 137739 and PI 294994, in addition to no significant differences among the three PIs in plant biomass reduction, suggested PI 262660 was a tolerant line, while PI 137739 and PI 294994 were antibiotic lines. Plant tolerance could not be elucidated among the three Betta isolines using aphid fecundity and plant biomass reduction as indicators.
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  • 8
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    Entomologia experimentalis et applicata 89 (1998), S. 111-118 
    ISSN: 1570-7458
    Keywords: leaf surface wax ; probing behavior ; nymphoposition ; Russian wheat aphid ; wheat ; barley ; oat ; Homoptera ; Aphididae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The effect of cereal leaf surface wax on Diuraphis noxia (Mordvilko), the Russian wheat aphid, probing behavior and nymphoposition was evaluated. Ultrastructure of leaf epicuticular wax from wheat (Triticum aestivum L.) c.v. ‘Arapahoe’ and ‘Halt’ was different from barley (Hordeum vulgare L.) c.v. ‘Morex’, and oat (Avena sativa L.) c.v. ‘Border’. Both wheat cultivars had similar rod-shaped epicuticular wax, while barley and oat plants had flakes. The chemical composition comparison of gas chromatograms also indicated that the extract of the two wheat cultivars had similar pattern of peaks, while the barley and oat leaves had similar peaks. Cereal variety significantly affected aphid probing behavior (P 〈 0.05), but wax removal using ethyl ether swab did not (P 〈 0.05). Aphids initiated significantly more probes on Border oat leaves than on Morex barley irrespective of wax removal, although total probing duration per aphid was not significantly different among the four cereals examined. Accumulative salivation duration per aphid on oat leaves with wax was significantly longer than other cereal leaves with wax, while accumulative ingestion duration per aphid on Arapahoe wheat and Morex barley was significantly longer than on oat. Nymphoposition of D. noxia on cereal leaves maintained on the benzimidazole-agar medium showed that aphids produced a greater number of nymphs on Morex barley and less on Border oat leaves, although wax removal did not affect aphid nymphoposition. Removal of leaf epicuticular waxes from the 4 cereal genotypes using ethyl ether swab indicated that the influence of wax on plant resistance to D. noxia probing and reproduction was limited. Morex barley was the most favorable, while Border oat was the least favorable cereal host of D. noxia.
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  • 9
    ISSN: 1570-7458
    Keywords: sieve element ; salivation ; aphid ; plant resistance ; wheat ; Sitobion fragariae ; Triticum aestivum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Extended sieve element salivation (E1 waveform in the electrical penetration graph) is a characteristic activity during early sieve element punctures, particularly in resistant plants. In order to explore a chemically-mediated mechanism of resistance associated with sieve element salivation, we compared the pattern of feeding behaviour of the aphid, Sitobion fragariae (Walker), on two cultivars of the wheat Triticum aestivum L., with different concentrations of hydroxamic acids (Hx). During 24 h of electronic monitoring, aphids dedicated over 50% of the total time to phloem ingestion from the sieve elements. Total time allocated to E1 in the experiment, time to first E1 within the experiment, time allocated to E1 before a sustained phloem ingestion (E2) and the contribution of sieve element salivation to the phloem phase (E1/[E1+E2]) were significantly higher in the high-Hx cultivar. The increased salivation in plants with higher contents of Hx suggests the existence, at least in this system, of a chemically-mediated sieve element constraint.
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  • 10
    Electronic Resource
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    Springer
    Cellular and molecular life sciences 50 (1994), S. 571-575 
    ISSN: 1420-9071
    Keywords: Ancient DNA ; archaeobotany ; carbonized grain ; DNA sequences ; glutenin alleles ; seed proteins ; Triticum ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have used hybridization analysis to detect ancient DNA in wheat seeds collected from three archaeological sites in Europe and the Middle East. One of these samples, carbonizedT. spelta dated to the first millennium BC, has yielded PCR products after amplification with primers directed at the leader regions of the HMW (high molecular weight) glutenin alleles. Sequences obtained from these products suggest that the DNA present in the Danebury seeds is chemically damaged, as expected for ancient DNA, and also indicate that it should be possible to study the genetic variability of archaeological wheat by ancient DNA analysis. Finally, we describe a PCR-based system that enables tetraploid and hexaploid wheats to be distinguished.
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  • 11
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    Plant molecular biology reporter 17 (1999), S. 323-331 
    ISSN: 1572-9818
    Keywords: Agrobacterium ; modular vector ; transformation ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Wheat (cv Chinese Spring) tissues were transformed using Agrobacterium tumefasciens and a new plasmid modular vector, pMVTBP. We constructed pMVTBP with unique restriction sites connecting (1) the CaMV 35S promoter, (2) a Kozak sequence, (3) the FLAG epitope, (4) the (His)6 epitope, (5) a coding region (for wheat TATA Binding Protein, wTBP) and (6) the CaMV 35S 3′UTR. This vector thus allows easy exchange of different regulatory or coding sequences. Explants of either germinating mature seeds, or immature embryos, were induced to callus for up to two weeks, treated with virulence-induced bacteria for one hour, then regenerated into plantlets. Transient expression of a GUS reporter gene, assayed at about one week, occurred in 10–12% of calluses. Expression of the FLAG-tagged wTBP was also detected, by immunostaining. Stable expression, by selective growth on geneticin, and by GUS expression at about six weeks, occurred in 1–2% of calluses, quite comparable to that achieved by other methods.
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  • 12
    ISSN: 1573-0832
    Keywords: deoxynivalenol ; enzyme immunoassay ; feed ; maize ; mycotoxins ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Samples of wheat (n = 25) and maize (n = 30) for animal consumption, collected in 1997 after harvest from western Romania, were analyzed by enzyme immunoassays for mycotoxin contamination. Toxins analyses included deoxynivalenol (DON), 3-acetylDON, 15- acetylDON, fusarenone X (FX), T-2 Toxin (T-2), diacetoxyscirpenol (DAS), zearalenone (ZEA), fumonisin B1 (FB1), aflatoxin B1 (AFB1), ochratoxin A (OA), and citrinin (CT). DON and acetylDONs were the major contaminants in wheat (100%) and maize (46%). Median values for DON, 3-acetylDON, and 15-acetylDON were 880 μg kg-1, 66 μg kg- 1, and 150 μg kg-1 in wheat, and 890 μg kg-1, 180 μg kg-1, and 620 μg kg- 1 in maize, respectively. Additionally, 3,15-diacetylDON was detected in some samples by HPLC-EIA analysis. All samples were negative for FX (〈150 μg kg-1). T-2 was found in wheat (n = 6) and maize (n = 1) at levels between 13 and 63 μg kg- 1. DAS (2.6 μg kg-1) was found in one maize sample. ZEA occurred in all wheat and in four maize samples, median values were 10 μg kg-1 and 250 μg kg-1, respectively. One maize sample contained FB1 (140 μg kg-1). All samples were AFB1-negative (〈4 μg kg-1). OA was found in one wheat sample (37 μg kg- 1), CT was found in one maize sample (580 μg kg- 1). This first reported natural occurrence of a range of mycotoxins in Romanian feeding stuff shows that DON and acetyl DONs may be present at levels which may affect animal production.
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  • 13
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    Mycopathologia 111 (1990), S. 181-189 
    ISSN: 1573-0832
    Keywords: mycotoxin ; ochratoxin ; Penicillium ; storage ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Eleven-kilogram parcels of HY-320 wheat, a cultivar of the new Canada Prairie Spring class, were kept at 15 and 19% initial moisture contents (IMC) in simulated storage in a Manitoba farm granary for 60 weeks to determine biotic and abiotic changes and mycotoxin production. Ochratoxin A reached a maximum of 0.24 ppm by week 20 in the 19% IMC wheat, but was absent in the 15% IMC wheat; no other mycotoxins were detected. Temperature, moisture content, O2 and CO2 levels, fat acidity values, seed germination, microfloral incidence and abundance, and the presence of other mycotoxins were monitored. Principal component analysis of all variables showed that the first principal components accounted for 32–41% of the system variability, and contained the ochratoxin A variable. Ochratoxin A was produced in moist grain that had decreased seed germination andAltermaria activity, and high fungal activity byPenicillium andAspergillus versicolor. Compared to other stored cereals previously studied, HY-320 wheat would be ranked in a low-risk category for mycotoxin formation, based on the ochratoxin A levels observed.
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  • 14
    ISSN: 1573-0832
    Keywords: Penicillium griseofulvum ; patulin ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Sixty-four wheat samples from Spanish flour factories were screened for patulin and patulin-producing moulds. None of them was found to contain any patulin, whereas samples experimentally contaminated with this toxin proved it to be highly unstable. On the other hand, Penicillium griseofulvum was the only in vitro patulin-producing species found (19 samples). Mould growth in the samples was investigated by using yeast-sucrose medium (YES) and high-performance liquid chromatography (HPLC) to measure the amounts of toxin produced during 40 day's incubation at 20 and 28°C. The highest yield rate of patulin was obtained between the 20th and 30th day of incubation; such a rate, however, was very low throughout the vigorous growth phase, during the first 20 days of incubation. The more appropriate temperature for incubation and patulin production was 28 °C. We also investigated the influence of other incubation conditions in the yield and found stationary dark cultures to be more efficient that shaken or fermentation cultures in YES medium. The best patulin yield achieved was 11.9 mg in the culture broth and 6.3 mg in the mycelium from 100 ml of medium.
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  • 15
    ISSN: 1573-0832
    Keywords: Fusarium ; mycotoxins ; occurrence ; trichothecenes ; wheat ; zearalenone ; deoxynivalenol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Wheat for human consumption (140 samples) was collected after harvest from all regions of Bulgaria. The 1995 crop year was characterized by heavy rainfall in the spring and summer months. The internal mycoflora of wheat samples was dominated by Fusarium spp. and Alternaria spp., and storage fungi were rarely present. The samples were analysed for contamination with Fusarium mycotoxins deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-AcDON), 15-acetyldeoxynivalenol (15-AcDON), T-2 Toxin (T-2), diacetoxyscirpenol (DAS), and zearalenone (ZEA), using enzyme immunoassay methods. DON and ZEA were the predominant toxins, with a contamination frequency of 67% and 69%, respectively. The average levels of these toxins in positive samples were 180 μg/kg (DON) and 17 μg/kg (ZEA), maximum concentrations were 1800 μg kg−1 and 120 μg kg−1, respectively. Acetyl derivatives of DON, namely 3-AcDON and 15-AcDON, were found in 2.1 % and 0.7% of the samples, at at maximum level of about 100 μg kg−1. Only one sample was positive for T-2 (55 μg/kg), DAS was not detected. This is the first report about the natural occurrence of a range of Fusarium mycotoxins in wheat for human consumption in Bulgaria.
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  • 16
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    Nutrient cycling in agroecosystems 40 (1994), S. 175-183 
    ISSN: 1573-0867
    Keywords: Nitrogen response ; on-farm research ; risk ; probability ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract In many developing countries, fertilizer recommendations must be made in the absence of plant and soil analyses. When the region is variable in terms of soils, weather, and magnitude of response to fertilizer, a recommendation is likely to involve a high degree of risk for the farmer. Quantification of such risk is key to developing appropriate recommendations for the farmer. However, most methodologies generally used in analyzing fertilizer trials do not allow adequate quantification, especially as a continuous function, of the risk associated with a given recommendation. Three years of on-farm trials conducted in the High Valley of Mexico were used to evaluate different methodologies for generating N fertilization recommendations and their associated risk for wheat (Triticum aestivum) production in the absence of soil tests. When the traditional approach, using average yield responses or separate trial results, was used, an economic optimum was identified, but it was not possible to quantify the associated risk. In contrast, however, by using a combination of response surface methodology and simple probability analysis, the risk associated with any given recommendation was developed, even under the highly variable conditions of the study zone. The approach uses a treatment difference matrix (developed using average yield differences between a treatment and the zero N (0N) check) and its associated standard deviation over locations. From the matrix, an equation (being a function of N rate and relative grain:N price ratios) was developed that shows the probability of outperforming the 0N check for the economic optimum rate.
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  • 17
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    Nutrient cycling in agroecosystems 29 (1991), S. 163-172 
    ISSN: 1573-0867
    Keywords: Superphosphate ; residual value ; sandy soil ; leaching of phosphorus ; lupins ; barley ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract In a field experiment on deep, yellow, sandy soil near Badgingarra, Western Australia, the residual value of superphosphate applied one and two years previously was measured relative to freshly-applied superphosphate using yields of narrow-leafed lupin (Lupinus angustifolius), barley and wheat. In addition, soil samples were collected for measurement of bicarbonate-extractable soil P. This was also used to estimate the residual value of the superphosphate. For lupins and wheat, and for bicarbonate-extractable soil P, the residual value decreased with increasing level of application. For barley grain, the residual value was not significantly affected by the level of application. The decrease in residual value of superphosphate with increasing level of application is attributed to increased leaching of applied phosphorus (P) down the profile of the sandy soils as the level of application increases. This may reduce subsequent plant yields due to the delay in seedling roots reaching the P in the soil during the crucial early stages of plant growth. For lupins, the relationship between yield and the level of superphosphate applied was markedly sigmoidal. The relationship for wheat and barley was exponential. Consequently, at suboptimal levels of P application, lupins required about two to three times more P than wheat or barley to produce the same yield. However, lupins required less P to achieve near-maximum yield.
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  • 18
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    Nutrient cycling in agroecosystems 31 (1992), S. 319-329 
    ISSN: 1573-0867
    Keywords: Superphosphate ; fertilizer effectiveness ; residual value ; lupins ; oats ; wheat ; grain production ; bicarbonate-extractable soil phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract In a field experiment on a deep pale-yellow sand in a 600 mm per annum rainfall Mediterranean environment of south-western Australia, six levels of phosphorus (P) as superphosphate (O up to 546 kg P ha−1) were applied once only, to the soil surface, before sowing lupins (Lupinus angustifolius). The lupins were grown in a continuous arable cropping rotation with, in successive years, oats (Avena sativa), wheat (Triticum aestivum), lupins. Five such rotations were started in the experiment from 1985 to 1989. The experiment continued until the end of 1990. The relationship between lupin seed (grain) yields and the level of P applied was measured in the year of P application for five successive years (1985 to 1989). The relationship had the same general form but it varied between years, largely due to different maximum yields (yield plateaux) in each year. The residual value of superphosphate applied three years previously was measured for lupins on two occasions (1988 and 1989) relative to superphosphate applied in the current year. The residual values was different in the two years. The superphosphate applied three years previously was about 30% as effective as freshly applied superphosphate in 1988, and 12% as effective in 1989. At each harvest, the relationship between grain yield and the P concentration in the grain differed for different species. However, for each species at each harvest, the relationship was similar regardless of when the P was applied in the previous years. Thus each species had the same internal efficiency of P use curve, and yields varied only with P concentration in tissue. Bicarbonate-extractable soil P was determined on soil samples taken in mid-July of 1989 and 1990. These soil test values were related to grain yields at harvest. The relationship between yield and soil test values had the same general form but varied for different species within years and for each species between years. It also varied for each species within years depending on the year the P was applied.
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  • 19
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    Nutrient cycling in agroecosystems 31 (1992), S. 331-340 
    ISSN: 1573-0867
    Keywords: Superphosphate ; residual value ; wheat ; lupins ; soil test for phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract In a field experiment on a sandplain soil in a low rainfall (326 mm per annum) Mediterranean environment of south-western Australia, the effectiveness of superphosphate applied in 1986 was measured in three subsequent years relative to freshly-applied superphosphate each year, using grain (seed) yields of wheat (Triticum aestivum) and lupins (Lupinus angustifolius). The wheat and lupins were grown in rotation and both crops were grown each year starting in 1986. Bicarbonate-soluble phosphorus was determined on soil samples taken in mid June from where the P treatment was applied in 1986 only. These soil test values were related to the grain yields produced that year. For each level of superphosphate applied in 1986, soil test values decreased with increasing time from application. The relationship between grain yield and soil test values had the same general form within each year for both plant species, but varied between years. For both species, the effectiveness of superphosphate decreased by about 70–80% between the year of application and the first and second years after application, and by a further approximate 10% in the third year. The relationship between grain yield and the level of superphosphate applied became sigmoidal by 1989.
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  • 20
    ISSN: 1573-0867
    Keywords: nitrogen fertilizer rate ; electroultrafiltration ; wheat ; soil test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The objective of the investigation was to examine whether there exist relationships between the optimum nitrogen fertilizer rate for winter wheat and soil nitrogen fractions extracted by electroultrafiltration (EUF) from autumn samples of the upper soil layer (0–30 cm). Optimum nitrogen fertilizer rates were derived from grain yield curves of field trials carried out with increasing nitrogen fertilizer rates on 19 different sites in 1985/86 and 1986/87. Most soils were luvisols derived from loess, two soils were brown earths and one a pararendzina. Total Nitrogen fertilizer rates were 0, 40, 80, and 120 kg N/ha applied twice before ear emergence. The final nitrogen rate at ear emergence was the same for all treatments, namely 60 kg N/ha. Optimum nitrogen fertilizer rates were derived from the grain yield curve fitted to a modified Mitscherlich equation. The optimum nitrogen fertilizer rates were correlated with the nitrogen fractions extracted by EUF. The regression equation thus obtained showed that NO 3 - , the organic N fraction (EUF Norg), and the EUF Norg-quotient each had a highly significant impact on the optimum nitrogen fertilizer rate. The higher the amounts of EUF-N extracted the lower the optimum nitrogen rate. Substituting the EUF Norg-fraction for total nitrogen concentration in the upper soil layer gave a poorer relationship between the optimum nitrogen fertilizer rate and the soil data. In absolute terms the EUF Norg-fraction had by far the greatest impact on calculating the optimum nitrogen fertilizer rate. The investigation shows that the EUF method is a suitable technique for the determination of available soil nitrogen from which optimum nitrogen fertilizer rates can be derived for winter wheat cultivated under soil and climatic conditions typical for cereal growing areas in central Europe.
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  • 21
    ISSN: 1573-0867
    Keywords: 15N ; non-nod beans ; quantification of N2 fixation ; reference crops ; simulation technique ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: 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.
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    Nutrient cycling in agroecosystems 45 (1995), S. 209-215 
    ISSN: 1573-0867
    Keywords: climate ; fertilizer recovery ; 15N fertilizer ; precipitation-evaporation quotient ; soil ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: 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.
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  • 23
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    Nutrient cycling in agroecosystems 46 (1996), S. 225-234 
    ISSN: 1573-0867
    Keywords: long-term experiment ; maize ; wheat ; fertilizers ; farm yard manure ; weedicide application ; yield sustainability ; zinc deficiency ; nutrient uptake ; cropping sequence ; organic carbon build-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Long-term field experiments play an important role in understanding the complex interactions of plants, soils, climate and management and their effects on sustainable crop production. A long-term fertilizer experiment with maize-wheat-cowpea (fodder) is in progress since 1971 at Punjab Agricultural University farm Ludhiana, India. The experimental result for the first 21 years showed that application of N alone or in combination with P did not produce as much maize and wheat grains as the application of N, P and K together. Eight years after the start of the experiment, the optimal levels of N, P and K application (100% NPK) were unable to sustain the similar (maize) yield level as before because of Zn deficiency. Whereas in FYM amended plots the Zn deficiency did not appear and the higher crop yields could be sustained. The chemical control of weeds could not sustain the maize productivity at the same level as the manual removal of weeds. It was concluded that the high level of crop production can be sustained with the application of N, P and K under intensive cropping system provided deficiency of any of the micronutrient does not crop up. The deficiency of Zn is most likely to occur in semi-arid light textured alluvial soils under intensive cropping without the addition of farm yard manure/organic manures. In maize based cropping systems, manual control of weeds may be preferred to the chemical one. Addition of FYM in conjunction with 100% NPK is most beneficial both from bio-physical and economic point of view.
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  • 24
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    Nutrient cycling in agroecosystems 40 (1994), S. 207-214 
    ISSN: 1573-0867
    Keywords: available P ; citrate insoluble P ; phosphorus sources ; triple superphosphate ; Triticum aestivum ; water soluble P ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract A greenhouse study was conducted to determine if soil pH affects the requirement for water-soluble P and the tolerance of water-insoluble impurities in TSP fertilizers. Two commercial TSP fertilizers were selected to represent a range in phosphate rock sources and impurities. Phosphate fertilizer impurities were isolated as the water-washed fraction by washing whole fertilizers with deionized water. TSP fertilizers with various quantities of water-soluble P (1.2 to 99% water-soluble P) were simulated by mixing the water-washed fertilizer fractions or dicalcium phosphate (DCP) with reagent-grade monocalcium phosphate (MCP). The fertilizers were applied to supply 40 mg AOAC available P kg−1 to a Mountview silt loam (fine-silty, siliceous, thermic Typic Paleudults). Wheat (Triticum aestivum (L.)) was harvested at 49 and 84 days after planting. Soil pH values at the final forage harvest were 5.4±0.16 and 6.4±0.15. At a soil pH of 5.4, the TSP fertilizers required only 37% water-soluble P to reach maximum yields while at pH 6.4 the fertilizers required 63% water-soluble P. Results of this study show that higher levels of water -insoluble P can be tolerated in TSP fertilizers when applied to acid soils. Phosphorus uptake was not affected by soil pH, but for the mixtures containing the fertilizer residues the source having the lowest level of Fe and Al had a higher relative agronomic effectiveness.
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  • 25
    ISSN: 1573-0867
    Keywords: millet ; sorghum ; rice ; maize ; wheat ; nutrient harvest index ; post-anthesis nutrient uptake ; recovery fraction ; simulation modelling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: 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.
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    Nutrient cycling in agroecosystems 44 (1995), S. 217-223 
    ISSN: 1573-0867
    Keywords: foliar fertilizer ; nitrate ; potassium ; urea ; wheat ; yield
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: 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.
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  • 27
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    Nutrient cycling in agroecosystems 53 (1999), S. 139-146 
    ISSN: 1573-0867
    Keywords: critical levels of Mn ; soil extractants ; Mn-deficiency ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Seven chemical extractants were tested for their relative performance to predict the response of wheat to Mn application in coarse textured alkaline soils of semi-arid region. Five out of the seven extractants were found to be promising for the estimation of critical level of available Mn in these soils, as the amount of Mn extracted by these extractants was positively and significantly correlated with relative grain yield as well as Mn uptake. The critical deficiency level of soil available Mn with 0.005 M DTPA, 0.02% hydroquinone, 0.02 N sodium pyrophosphate, 0.1N H3PO4 and 0.05N HCl+0.025N H2SO4 was 3.1, 13.8, 23.5, 5.3 and 17.8 mg kg-1 soil, respectively. The 1N ammonium acetate and 0.01M CaCl2 were found to be unsuitable extractants for these soils. Further field trials at eight locations with varying levels of Mn deficiency showed successive increase in the grain yield of wheat with foliar Mn application, emphasizing the need for Mn fertilization when wheat is grown on Mn deficient soils.
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  • 28
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    Nutrient cycling in agroecosystems 58 (2000), S. 131-139 
    ISSN: 1573-0867
    Keywords: automated closed chamber method ; wheat ; cowpea ; slow-release nitrogen fertilizer ; residue management ; denitrification ; methane sink ; rainfall
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Rainfed rice (Oryza sativa L.)-based cropping systems are characterized by alternate wetting and drying cycles as monsoonal rains come and go. The potential for accumulation and denitrification of NO3 − is high in these systems as is the production and emission of CH4 during the monsoon rice season. Simultaneous measurements of CH4 and N2O emissions using automated closed chamber methods have been reported in irrigated rice fields but not in rainfed rice systems. In this field study at the International Rice Research Institute, Philippines, simultaneous and continuous measurements of CH4 and N2O were made from the 1994 wet season to the 1996 dry season. During the rice-growing seasons, CH4 fluxes were observed, with the highest emissions being in organic residue-amended plots. Nitrous oxide fluxes, on the other hand, were generally nonexistent, except after fertilization events where low N2O fluxes were observed. Slow-release N fertilizer further reduced the already low N2O emissions compared with prilled urea in the first rice season. During the dry seasons, when the field was planted to the upland crops cowpea [Vigna unguiculata (L.) Walp] and wheat (Triticum aestivum L.), positive CH4 fluxes were low and insignificant except after the imposition of a permanent flood where high CH4 fluxes appeared. Evidences of CH4 uptake were apparent in the first dry season, especially in cowpea plots, indicating that rainfed lowland rice soils can act as sink for CH4 during the upland crop cycle. Large N2O fluxes were observed shortly after rainfall events due to denitrification of accumulated NO3 −. Cumulative CH4 and N2O fluxes observed during this study in rainfed conditions were lower compared with previous studies on irrigated rice fields.
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  • 29
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    Nutrient cycling in agroecosystems 21 (1990), S. 163-166 
    ISSN: 1573-0867
    Keywords: Critical level of Zn ; alkaline soils ; Zn-deficiency ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Field experiments were conducted at 32 locations, chosen for their wide range in DTPA extractable Zn, to determine the critical deficiency level of Zn for predicting response of wheat to Zn application. Soil application of 5.6 kg Zn ha−1 significantly increased the grain yield in deficient soils. Soil extractable Zn was significantly related with per cent grain response and absolute grain yield. Both the graphical and statistical methods of Cate and Nelson indicated the critical level to be 0.75 mg kg−1 soil of DTPA extractable Zn. This level gave a predictability value of 82 per cent.
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  • 30
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    Nutrient cycling in agroecosystems 22 (1990), S. 147-159 
    ISSN: 1573-0867
    Keywords: Sulfate ; elemental sulfur ; leaching ; ryegrass ; wheat ; greenhouse experiments ; split application
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Three factorial experiments with four replications were conducted in a greenhouse to examine the effectiveness of gypsum, elemental sulfur (ES powder) and three S containing N fertilizers, viz., ammonium sulfate (AS), urea + ES, and Ureas (20% AS and 80% urea). All experiments were conducted twice in different years. In the first experiment with uncropped soil, the effects of soil type, leaching rate (2.3 and 6.9 mm water per day) and urea addition on sulfate leaching losses were studied. Leaching losses decreased in the order Ureas 〉 ammonium sulfate (AS) 〉 gypsum ≫ urea + ES. Increasing the leaching rate greatly increased sulfate losses from both soils. Losses were greater in the sandy Typic Hapludoll than in the clayey Oxic Paleustalf. Sulfate adsorption was found to decrease strongly with rising the pH in both soils. Hydrolysis of urea temporarily raised the pH of the soil, thereby increasing the sulfate leaching losses. In the second experiment the effects of S rate (0–65 mg per kg soil), split application and leaching rate (0 and 2.3 mm per day) on sulfate leaching losses and ‘apparent S recovery’ (ASR) by three successive cuts of ryegrass (Lolium perenne L.) were studied. Herbage yield more than doubled when S was applied. The effectiveness of the sulfate fertilizers was greater when S was split-applied than given all at once. With split applications the ASR decreased in the order: Ureas 〉 AS 〉 gypsum 〉 urea + ES 〉 ES powder. ES fertilizers were least effective, because the oxidation rate of ES to sulfate was clearly too slow. In the third experiment the effects of S rate (0–40 mg per kg soil) and split application on sulfate leaching losses and ASR in the grain of wheat (Triticum aestivum L.) were studied under leaching conditions (2.3 mm per day). Grain yield increased strongly due to S application. Split application greatly increased the effectiveness of the sulfate fertilizers and appeared to be an effective tool in satisfying the S need of the crop under leaching conditions. Again, ES fertilizers were least effective, because the oxidation rate of ES was too slow to meet the S demand of the crop. In all experiments leaching losses of sulfate from the ES fertilizers were smaller than from the sulfate fertilizers.
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  • 31
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    Nutrient cycling in agroecosystems 22 (1990), S. 97-107 
    ISSN: 1573-0867
    Keywords: Superphosphate ; placement depth ; banding ; relative effectivenesss ; lupins ; wheat ; field experiment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract In a field experiment on a sandplain soil in a low rainfall (326mm per annum) Mediterranean environment of south-western Australia, seven levels of single superphosphate, 0, 7.5, 10, 14, 19.5, 30 and 39 kg P ha−1, were placed at either 3, 5, 7, 9, 11 or 13 cm depth before sowing wheat (Triticum aestivum) at 3 cm. In a separate treatment, superphosphate was drilled with the seed (the normal practice). In the second year, the plots were sown with lupins (Lupinus angustifolius) at 3 cm depth with no additional superphosphate. In three separate treatments, superphosphate at 0, 14 and 39 kg P ha−1, was drilled with the lupin seed (the normal practice) on plots that had received no superphosphate in the first year. Yields of wheat and lupins were used as a measure of the effectiveness of the superphosphate placement treatments relative to the effectiveness of superphosphate drilled with seed of wheat (year 1) or lupins (year 2), to give relative effectiveness (RE) values in each of the two years. In the first year the RE of superphosphate was increased by about 20% when the fertilizer was placed 5 to 9 cm deep in the soil. In the second year, the RE of superphosphate for producing lupin grain was increased by about 30–60% where the fertilizer had been placed 5–13 cm deep in the previous year compared with freshly drilled 3 cm deep. The yield of wheat or lupins was closely related to the P content of plant tissue; each relationship was independent of the depth or year of superphosphate application.
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  • 32
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    Nutrient cycling in agroecosystems 26 (1990), S. 229-235 
    ISSN: 1573-0867
    Keywords: Grass ; wheat ; nitrogen nutrition ; dilution curve ; mineral content ; mineral removal ; phosphorus ; potassium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The important effect of nitrogen in changing the patterns of mineral content and mineral removal is analysed for grass swards and wheat. Different models are proposed; accumulated dry matter developed throughout a growing period is shown to be an excellent reference for assessing the evolution of the plant mineral content and the mineral removal the growing crop. Applications in diagnosing mineral nutrition status and optimising fertilizer use are proposed and discussed.
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    Nutrient cycling in agroecosystems 39 (1994), S. 77-82 
    ISSN: 1573-0867
    Keywords: Acidic subsurface layer ; application rate ; North Carolina phosphate rock ; placement method ; time of application ; triple superphosphate ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Using soils with an acidic subsurface layer, three glasshouse experiments were carried out to evaluate the effect of placement method and application rate of triple superphosphate (TSP) and North Carolina phosphate rock (NCPR) on dry matter (DM) yields. Time of application of NCPR on DM yield response of wheat was also studied. For Experiment 1, soil was collected in depth intervals of 0–2; 4–6; 6–8; and 8–10 cm from a red earth (chromic luvisol). The treatments included two P sources (TSP and NCPR), three placement methods (broadcast, banded or mixed into the subsurface layer, 6–8 cm), and six application rates. In this P deficient soil with an acidic subsurface layer, there was relatively little effect of application method of TSP on wheat yield responses. The maximum dry matter yield responses for broadcast, band and mix application methods was 30, 42 and 50 %, respectively. Responses to NCPR broadcast, band and mix methods were 20, 9 and 44 %, respectively. Mixing NCPR into to acidic subsurface layer produced yields similar to those from TSP although a higher application rate of P as NCPR was needed to achieve this outcome. Treatments for Experiments 2 and 3 were time of application of NCPR (0 and 30 days before sowing) and rate of application of NCPR (0 and 40 mg P/pot). In Experiment 2 (same soil as Experiment 1) application of NCPR prior to sowing, resulted in higher Colwell P concentration than when applied at sowing, but time of application had no effect on final DM yields. Experiment 3 used a red podzolic (chromic luvisol) soil which had a lower P-status, was more acid and had a lower exchangeable Ca2+ concentration than the red earth. Application of NCPR prior to sowing resulted in lower DM yield than when it was applied prior to sowing.
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  • 34
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    Nutrient cycling in agroecosystems 31 (1992), S. 43-49 
    ISSN: 1573-0867
    Keywords: Superphosphate ; nitrogen fertilizer ; take-all ; (Gaeumannomyces graminis) ; wheat ; Triticum aestivum L.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Wheat was grown continuously in soil amended with 5 levels of superphosphate and with 4 levels of urea at 3 sites. The incidence and severity of take-all, caused byGaeumannomyces graminis var.tritici, declined with increasing rates of application of both superphosphate and urea. In both years, the severity of take-all on plants receiving neither superphosphate nor urea was about 40% while at the highest level of superphosphate and urea supply the take-all severity was approximately halved at 22%. There was an increase in grain yield in response to applied superphosphate and urea to the highest level of each nutrient. There was also an increase in the 1,000-kernal weights with superphosphate and urea fertilizer application.
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  • 35
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    Nutrient cycling in agroecosystems 32 (1992), S. 27-36 
    ISSN: 1573-0867
    Keywords: Phosphorus requirement ; wheat ; oats ; barley ; lupins ; triticale ; superphosphate ; grain yield ; phosphorus in grain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The phosphorus (P) requirement for grain production of different crop species (oats (Avena sativa), barley (Hordeum vulgare), triticale (xTriticosecale), narrow-leafed lupins (Lupinus angustifolius), and sandplain lupins (L. cosentinii) was compared with wheat (Triticum aestivum) in five field experiments on different lateritic soils in south-western Australia. Seven or eight levels of superphosphate were applied at the start of each experiment. The amount of P required to produce 70% (four experiments) or 90% (one experiment) of the maximum yield was used to compare P requirements. Large differences in the P requirements of the species were obtained. On P deficient soil in 3 experiments, oats required from 50 to 70% less P than wheat, but required 40% more P on a soil with a long history of superphosphate applications. Compared with wheat, in the year of P application, barley required 50% less P in one experiment, had similar P requirements in two experiments, and required 80% more P in another experiment. In the years after P application, barley required 20% less P in two experiments. On an acidic soil triticale required from 50% to 70% less P than wheat, but on less acidic soil it required 100% more P. In the year of P application, narrow-leafed lupins required 800% more P than wheat in one experiment, and 30% more P in the other experiment. In the year of P application, sandplain lupins required 70% less P than wheat in one experiment.
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    Nutrient cycling in agroecosystems 32 (1992), S. 185-194 
    ISSN: 1573-0867
    Keywords: Residual P ; P fixation ; Bray P ; Olsen P ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Nineteen soils from the south east of the Province of Buenos Aires (Argentina) that had been fertilized with moderate amounts of P (10–40 kgP/ha) during the last 10 years were used to investigate the effect of time on the decline of P availability as measured by three soil tests (Bray 1, Bray 2, Olsen) and the null-point method. Differences in rates of P decline among soils and chemical methods were characterized by an exponential coefficient for time (b 2) in equations which describe the changes of the added P retained by the soil (Pr =ac b1 t b2). The rate of decline of P for the nineteen soils calculated for the soil test methods was ordered decreasingly as: null-point 〉 Olsen 〉 Bray 1 〉 Bray 2. The ability of the chemical methods for assessing the residual value of P for wheat growth (RV) was tested in a pot experiment on seven of the soils that differed in their individual rates of reaction with P. Differences between soils in the rate of reaction with P as measured in the laboratory by the null-point method and by the Olsen test were reflected in different residual values for P fertilizer for wheat plants. Thus the value ofb 2 for these methods was well correlated with the observed residual values. The soil properties commonly associated with the retention of P were not related to the value ofb 2 suggesting that more than one soil property may be involved in the measure ofb 2. The exponent for timeb 2 may be used as an index of the ability of the soil test to reflect the decline of P availability with time.
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    Nutrient cycling in agroecosystems 39 (1994), S. 11-18 
    ISSN: 1573-0867
    Keywords: Copper fertiliser ; nitrogen fertiliser ; residual effectiveness ; Triticum aestivum L. ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The residual effectiveness of copper (Cu) applied 18 to 21 years previously was estimated for grain yield of wheat. In one field experiment, current levels of Cu fertiliser were applied and its effectiveness was compared to that of the same level of Cu applied previously. The effects of nitrogen (N) fertiliser on the Cu concentration in the youngest emerged blade and in the grain, as well as the effects of N levels on the grain yield of wheat, were also studied. Where the recommended level of Cu fertiliser had been applied previously, its residual effectiveness depended on the soil type. On the grey sands over clay and gravelly sands over clay, the residual Cu would last approximately 20 years where wheat is grown in rotation with a legume crop (Lupinus augustifolius L.) and where N fertiliser is applied at high levels (92 kg N ha−1). On the yellow brown sandy earths of the Newdegate district, the residual value was in excess of 30 years. When Cu levels in the soil are marginal, high levels of N applied to wheat crops grown on stubbles of legume crops (high soil N) could suffer from induce Cu deficiency which could reduce grain production. Critical concentrations of Cu in the youngest emerged blade of less than 1.2 mg Cu kg−1 at Gs50–59 would indicate Cu deficiency. Cu concentrations of less than 1.1–1.2 mg Cu kg−1 in the grain suggest that the wheat crop is marginally supplied with Cu. In both situations, Cu fertiliser needs to be applied before the next crop.
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  • 38
    ISSN: 1573-0867
    Keywords: Cochliobolus sativus ; common root rot ; Penicillium bilaji ; phosphorus fertilization ; tillering ; wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract A strain ofPenicillium bilaji Chalabuda (PB) has recently been commercially released as a seed inoculant to increase phosphorus (P) uptake by wheat (Triticum aestivum L.). The purpose of this study was to compare the effects of drill applied P (15 kg P ha−1) with PB seed inoculation on early growth, development, P uptake, and grain yield of ‘Stoa’ spring wheat at four sites in North Dakota. Fertilization with P consistently enhanced early season growth, main stem development, tillering and P uptake. Seed inoculation with PB had little or no effect on these traits. Phosphorus fertilization tended to increase common root rot severity (CRR, incited byCochliobolus sativus (Ito & Kurib) Drechs.), while PB inoculation had no effect. Grain yields were significantly increased by P fertilization at one location. Inoculation with PB also increased grain yield at this location. The reason why PB inoculation increased yield at this location is not evident, as plant growth and P uptake were not enhanced earlier in the season. Averaged across all four sites, PB inoculation increased wheat yields 66 kg ha−1, which is similar to averaged yield responses reported from the Prairie Provinces of Canada.
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  • 39
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    Nutrient cycling in agroecosystems 45 (1995), S. 163-167 
    ISSN: 1573-0867
    Keywords: Basal dressing ; Se-enriched fertilizers ; Se-uptake ; soil texture ; top-dressing ; wheat
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: 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.
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  • 40
    ISSN: 1572-9699
    Keywords: bioluminescence ; Pseudomonas ; root colonization ; wheat
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    Topics: Biology
    Notes: Abstract The bioluminescently marked Pseudomonas fluorescens strain 5RL, has been used previously to follow colonisation of soy bean roots (De Weger et al. [1991] Appl. Environ. Microbiol. 57:36-41). In the present paper the method has been further developed and optimized for wheat roots and it is used to get a quick overview of the colonisation patterns of many different root systems at the same time. Colonisation was followed on wheat plants grown in our gnotobiotic sand system (Simons et al., 1996. Mol Plant Microbe Interact 9: 600–607) and the following results were obtained. (i) A spatio-temporal analysis of the colonisation of wheat roots showed that 4 days after planting the highest bacterial activity was observed at the upper part of the root. After 6 days the high bacterial activity at the upper part was further increased, whereas spot-like activities were observed on the lower root parts, possibly due to micro-colonies. (ii) Bacterial mutations causing lack of motility or auxotrophy for amino acids resulted in impaired colonisation of the lower root parts, indicating that motility and prototrophy for the involved amino acid(s) are important factors for wheat root colonisation by strain 5RL. (iii) Coinoculation of strain 5RL with other wild type Pseudomonas strains on the root influenced the colonisation pattern observed for strain 5RL. Colonisation was not visually affected when the competing strain was a poor root coloniser, but was severely reduced when the competing strain was a good root coloniser. The results show that the spatio-temporal colonisation of wheat root by P. fluorescens strain 5RL and derivatives is similar to that of strain WCS365 on tomato. The advantage of the use of lux-marked strains is that the results are obtained much quicker than when conventional methods are used and that the result is supplied as an image of the colonisation pattern of many different roots.
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  • 41
    ISSN: 1572-9761
    Keywords: Coccinellidae ; Aphididae ; wheat ; spatial scale ; species diversity ; numerical response
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    Topics: Biology
    Notes: Abstract The influence of prey density, within-field vegetation, and the composition and patchiness of the surrounding landscape on the abundance of insect predators of cereal aphids was studied in wheat fields in eastern South Dakota, USA. Cereal aphids, aphid predators, and within-field vegetation were sampled in 104 fields over a three year period (1988–1990). The composition and patchiness of the landscape surrounding each field were determined from high altitude aerial photographs. Five landscape variables, aggregated at three spatial scales ranging from 2.6 km2 to 581 km2, were measured from aerial photographs. Regression models incorporating within-field and landscape variables accounted for 27–49% of the variance in aphid predator abundance in wheat fields. Aphid predator species richness and species diversity were also related to within-field and landscape variables. Some predators were strongly influenced by variability in the composition and patchiness of the landscape surrounding a field at a particular spatial scale while others responded to variability at all scales. Overall, predator abundance, species richness, and species diversity increased with increasing vegetational diversity in wheat fields and with increasing amounts of non-cultivated lands and increasing patchiness in the surrounding landscape.
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  • 42
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    Integrated pest management reviews 4 (1999), S. 127-143 
    ISSN: 1572-9745
    Keywords: wheat ; stored-grain ; integrated pest management ; aeration ; biological control ; grain sampling ; insect monitoring ; modeling ; area-wide IPM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Management of stored-grain insect pests by farmers or elevator managers should be based upon a knowledge of the grain storage environment and the ecology of insect pests. Grain storage facilities and practices, geographical location, government policies, and marketing demands for grain quality are discussed as factors influencing stored-grain insect pest management decisions in the United States. Typical practices include a small number of grain samples designed to provide grain quality information for segregation, blending and marketing. This low sampling rate results in subjective evaluation and inconsistent penalties for insect-related quality factors. Information on the efficacy of insect pest management practices in the United States, mainly for farm-stored wheat, is discussed, and stored-grain integrated pest management (IPM) is compared to field-crop IPM. The transition from traditional stored-grain insect pest control to IPM will require greater emphasis on sampling to estimate insect densities, the development of sound economic thresholds and decision-making strategies, more selective use of pesticides, and greater use of nonchemical methods such as aeration. New developments in insect monitoring, predictive computer models, grain cooling by aeration, biological control, and fumigation are reviewed, their potential for improving insect pest management is discussed, and future research needs are examined.
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  • 43
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    Cellular and molecular life sciences 46 (1990), S. 1016-1017 
    ISSN: 1420-9071
    Keywords: In vitro absorption ; calcium ; wheat ; Bengal gram
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    Topics: Biology , Medicine
    Notes: Summary The in vitro absorption of calcium from the duodenum was significantly less in a group of rats fed on a wheat diet than in a group fed a wheat and Bengal gram (70∶30) diet.
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  • 44
    ISSN: 1432-203X
    Keywords: wheat ; rye ; embryogenesis ; growth ; tissue culture
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    Topics: Biology
    Notes: Summary The influence of the short arm of rye chromosome 1 (1RS) from Secale cereale var. Imperial on the growth and differentiation of callus cultures from wheat Triticum aestivum var. Chinese Spring immature embryos was analysed. This chromosome arm was found to stimulate both embryogenesis and the rate of growth of calli. Recombinant lines carrying segments of 1RS were used to delineate the regions of 1RS responsible for the tissue culture effects. The enhancement of embryogenesis and the stimulation of growth were shown to be associated with two distinct genetic regions of the chromosome arm; the former is located between the centromere and the Sec 1 locus, while the latter is situated in the immediate vicinity of the Sec 1 locus.
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  • 45
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    European journal of clinical pharmacology 42 (1992), S. 101-105 
    ISSN: 1432-1041
    Keywords: Rufloxacin ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma and urine kinetics of rufloxacin were assessed in healthy volunteers after single (100, 200, 400 and 800 mg) and multiple (300 mg followed by 150 mg daily, Group 1, and 400 mg followed by 200 mg daily, Group 2) oral doses. The kinetics of a single oral dose of 800 mg was assessed in fasting and non-fasting subjects to assess the influence of food intake on drug absorption. The AUCs were 134, 266 and 375 μg · h · ml−1 after 100, 200 and 400 mg, respectively. The AUC after 800 mg p. o. was 715 μg · h · ml −1 in fasting subjects and 614 μg · h · ml−1 in non-fasting subjects. The parameters of the model and the mean renal clearance values indicated some departure from linearity in rufloxacin kinetics. After multiple doses the plasma drug levels during the 6th treatment day were similar to those after the first dose in Group 1 and were about 30–40% higher after the first dose in Group 2. The half-lives after the last dose were much shorter than those estimated in the single dose studies (33–36 h and 50–80 h, respectively).
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  • 46
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    European journal of clinical pharmacology 42 (1992), S. 535-538 
    ISSN: 1432-1041
    Keywords: Meropenem ; Carbapenem ; pharmacokinetics ; uraemia ; haemodialysis
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of IV meropenem (500 mg over 30 min) has been studied in 6 healthy volunteers and 26 patients with various degrees of renal impairment. Blood samples were taken at different times over 24 h in healthy subjects and 36 to 48 h in uraemic patients, and four or five urine samples were collected over 24 or 48 h. Meropenem concentrations in plasma and urine were measured by a microbiological assay. The mean peak plasma concentration of meropenem ranged from 28 to 40 μg·ml−1 and was not affected by the degree of renal impairment. The terminal half-life of meropenem was approximately 1 h in subjects with normal kidney function and it was proportionately increased as renal function decreased. A significant linear relationship between total body clearance and creatinine clearance as well as between renal clearance and creatinine clearance was observed. The mean apparent volume of distribution at steady state was not significantly altered in uraemic patients. The mean cumulative urinary recovery of meropenem in healthy volunteers was 77% of the administered dose and it was significantly decreased in patients with renal impairment. Haemodialysis shortened the elimination half-life, from 9.7 h during the predialysis period to 1.4 h during the dialysis period. The dose of meropenem should be reduced in relation to the decrease in creatinine clearance.
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  • 47
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    European journal of clinical pharmacology 42 (1992), S. 559-560 
    ISSN: 1432-1041
    Keywords: Mefloquine ; Thai subjects ; pharmacokinetics ; Primaquine ; drug interaction ; adverse effects
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    Topics: Chemistry and Pharmacology , Medicine
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  • 48
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    European journal of clinical pharmacology 39 (1990), S. 395-397 
    ISSN: 1432-1041
    Keywords: atropine ; exercise ; pharmacokinetics ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven healthy males (19–32 y) underwent each of four separate conditions in a repeated measures design. Five of these subjects underwent an additional trial. In four of five trials subjects received 2.0 mg atropine sulfate intramuscularly in the anterolateral portion of the left thigh: at rest (T1); following completion of a single exercise (Ex) bout (T2), (Each bout consisted of 25 min of stationary cycling at 40% VO2 max with 5 min of seated rest), prior to three Ex bouts (T3) and following one and prior to three Ex bouts (T5). Trial 4 (T4) was the same as T3 with the substitution of a saline placebo. Serum samples were collected over a 12 h period and atropine concentration was determined by RIA. Ex trials were compared to T1. Ex prior to atropine (T2) significantly decreased the mean volume of distribution (Vz, 278 vs 2321). Ex in T3 significantly decreased the serum half life (t1/2, 4.2 vs 3.5 h), Vz (278 vs 1981), and clearance (CL, 763 vs 638 ml·min−1) and significantly increased the peak concentration (Cp, 6.7 vs 12.3 ng·ml−1) and area under the curve (AUC, 44.1 vs 53.1 ng·ml−1). In T5, Ex significantly decreased the t1/2 (3.4 h), Vz (182 l) and CL (575 ml·min−1) and significantly increased the absorption rate constant (ka, 0.482 vs 1.1 min−1), elimination rate constant (ke, 0.0012 vs 0.0015 min−1), Cp (14 ng·ml−1) and AUC (53.3 ng·h·ml−1). These results demonstrate that moderate Ex either prior to and/or immediately following drug administration has the capacity to significantly modify atropine pharmacokinetics.
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  • 49
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    European journal of clinical pharmacology 42 (1992), S. 689-691 
    ISSN: 1432-1041
    Keywords: Diphemanil methylsulphate ; pharmacokinetics ; healthy subjects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of oral diphemanil methylsulphate have been evaluated in six healthy male volunteers. Absorption of the drug was slow (tmax=2 to 4 h), the mean half-life was 8.35 h, and the amount of the drug recovered in urine within 48 h ranged from 0.6 to 7.4% of the administered dose. The results suggest low bioavailability, assuming that the drug is poorly metabolized.
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  • 50
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    European journal of clinical pharmacology 42 (1992), S. 693-694 
    ISSN: 1432-1041
    Keywords: Loperamide ; loperamide oxide ; diarrhoea ; pharmacokinetics ; dose-proportionality
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of loperamide, after oral administration of increasing doses (1 to 16 mg) of loperamide oxide, has been investigated in 10 healthy male volunteers, using a randomised cross-over design. Comparison of the maximum plasma loperamide concentration and AUC demonstrated that the bioavailability of loperamide was proportional to the dose of loperamide oxide administered.
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  • 51
    ISSN: 1432-1041
    Keywords: Alpidem ; Anxiolytics ; pharmacokinetics ; tolerance ; metabolites ; sedation ; adverse events
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, placebo-controlled, crossover experiment in 21 healthy male volunteers, aged 19 to 27 y, the pharmacokinetics and tolerance of the new anxiolytic drug alpidem (SL80.0342) and its three major metabolites were studied after single doses of 25, 50, 100 and 200 mg. Plasma concentrations of alpidem (in 20 subjects) and metabolites (in 6 subjects) were measured by HPLC over a period of 54 h after dosing. Cmax, tmax and AUC(0–54) and, when possible, t1/2 were determined for alpidem and metabolites and the dose linearity of the parameters was investigated. The time to peak of alpidem was dose independent in most subjects and was short (1–4 h); the mean values at the four dosing levels were 1.9, 1.7, 1.6 and 1.8 h. The peak concentration increased with the dose, the mean values being 17, 34, 88 and 115 ng · ml−1, respectively. In 50% of the subjects cmax tended to stabilize between the 100 and 200 mg dose. Dose linearity was also present for the AUC, which plateaued between the 100 and 200 mg dose in only 3 out of 20 subjects; the mean AUC was 119, 281, 669 and 1117 ng · ml−1 · h, respectively. The apparent half-life of elimination appeared to be dose independent, mean values at the increasing dosing levels being 18.7, 19.9, 18,1 and 17.9 h. A similar relationship between the kinetics parameters and dose of the alpidem was observed for the metabolites SL83.0912, SL80.0522 and SL83.0725. The formation of metabolites was not saturated as their AUCs relative to corresponding alpidem AUCs were not dose related. Thus the kinetics of alpidem and its three major metabolites were linear after doses of 25 to 200 mg. The drug was well tolerated by most of the subjects. Sedation and dizziness occurred mainly after the 100 and 200 mg doses.
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  • 52
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    European journal of clinical pharmacology 43 (1992), S. 67-75 
    ISSN: 1432-1041
    Keywords: Morphine ; Patient-controlled analgesia ; opioids ; pharmacokinetics ; bolus-elimination-transfer ; computer-assisted continuous infusion
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bone marrow transplant patients having severe, prolonged oral mucositis pain (expected to last for one to three weeks) used a computer-controlled infusion system to self-administer morphine for pain control. Individual patient pharmacokinetic information, derived from a pretreatment bolus morphine dose, was used in a new bolus-elimination transfer algorithm to produce rapid adjustments of steady plasma morphine concentrations when the patient requested more or less drug. We evaluated the performance characteristics (bias and precision) of this pharmacokinetically based patient-controlled analgesic infusion system (PKPCA) in a group of 15 cancer patients over six to 14 days. Although we found a three- to fivefold pharmaco-kinetic variability in the tailoring morphine dose data, the PKPCA system was free of systematic bias (insignificant overall prediction error) during the patient-controlled infusions in this study population. The absolute prediction error was 19.9% for the group on the first study day and 25.6% over the entire study period (aggregate results; 6–14 days of continuous use). Two-thirds of the patients exhibited no bias throughout the study period, and individual bias in the others was symmetrically distributed (three patients with underpredictions and two overpredicted). Magnitude of prediction error during the patient-controlled morphine infusions was not related to the magnitude of pharmacokinetic deviation of individual subjects from group parameters. Our results indicate that this PKPCA system provides accurate control of plasma morphine concentration when used by patients to self-administer opioid for prolonged pain relief continuously over 1 to 2 weeks. Use of individual pharmacokinetic information, instead of population parameters, may account for superior performance characteristic of this computer-assisted continuous drug infusion system.
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  • 53
    ISSN: 1432-1041
    Keywords: Indomethacin ; steady-state ; pharmacokinetics ; elderly
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady-state pharmacokinetic profile of indomethacin was examined in twelve healthy volunteers (4 m, 8 f; 20–34 y) and in 12 elderly subjects (7 m, 5 f; 70–88 y). Two formulations of indomethacin were examined, providing duplicate data for each subject group. The subjects received each formulation of indomethacin (25 mg tid) for 6 days in a single blind crossover fashion. On day 7, after an overnight fast, a final 25 mg dose of indomethacin was given and plasma concentrations measured over the following 12 h. Kinetic parameters Cpmin, tmx and AUC (0–12 h) were determined. There were no differences in the pharmacokinetic parameters between young and elderly subjects or between data for the two formulations of indomethacin. AUC values (μg · ml−1 · h), for example, for the two formulations in the young subjects were 5.85 and 6.85 while the values for the elderly subjects were 6.55 and 6.50 respectively. When each treatment period was considered independently there was a significant difference between young and elderly subjects with regard to compliance. The rates of non compliance (over and under compliance) using a capsule count technique were, however, low with a mean maximum value of 5.8% being recorded for the elderly subjects.
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  • 54
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    European journal of clinical pharmacology 41 (1991), S. 449-452 
    ISSN: 1432-1041
    Keywords: Diabetes mellitus ; Caffeine ; pharmacokinetics ; P-450 mono-oxygenase
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Diabetes may alter the pharmacokinetics of aminopyrine and antipyrine, which are used to assess liver function. Caffeine has recently been used to test liver function, but the effect of diabetes on caffeine kinetics is not known. The kinetics of caffeine has been examined in patients with decompensated Type I and Type II diabetes and in two age- and sex-matched control groups. In both types of diabetes the apparent caffeine clearance, half-life, and apparent volume of distribution were similar to controls. It is concluded that decompensated diabetes does not influence the cytochrome P-448 mono-oxygenase system responsible for caffeine metabolism.
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  • 55
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    European journal of clinical pharmacology 42 (1992), S. 231-233 
    ISSN: 1432-1041
    Keywords: Isradipine ; Haemodialysis ; pharmacokinetics ; dialysability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of isradipine, a calcium-channel blocker, have been studied in eight patients on chronic haemodialysis. A single oral dose of 5 mg was administered on both a non-haemodialysis and a haemodialysis day and the plasma concentrations of isradipine were analyzed. The mean cmax, tmax, AUC, and t1/2 in plasma on the non-haemodialysis day were 5.2 ng·ml−1, 1.4 h, 23.8 ng·h·ml−1, and 3.1 h, respectively. The dialysis clearance of isradipine was negligible (5.0 ml·min−1). The t1/2 values during haemodialysis were not significantly different from those observed during the same period post dose on the non-haemodialysis day. The study demonstrates that supplemental doses of isradipine are not necessary in these patients since isradipine is not significantly removed by haemodialysis.
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  • 56
    ISSN: 1432-1041
    Keywords: Liver cirrhosis ; Spirapril ; ACE inhibitor ; pharmacokinetics ; haemodynamic effects ; liver function tests
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and haemodynamic effects of orally administered spirapril, a novel angiotensinconverting enzyme (ACE) inhibitor, have been investigated in patients with liver cirrhosis (n=10), in patients with chronic, non-cirrhotic liver disease (n=8) and in a control group of healthy subjects (n=16). The absorption and elimination of spirapril did not differ between patients with liver disease and control subjects. In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 μg·h·l−1, 923 μg·h·l−1 and 1300 μg·h·l−1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively. Compared to healthy subjects, cirrhotic patients had a reduced rate constant of spiraprilat formation (1.10 h−1 in patients vs. 2.00 h−1 in control subjects) while the elimination half-life of spiraprilat was not different. The effect of spirapril on diastolic blood pressure was decreased in patients with chronic liver disease as compared to the controls. Thus, the pharmacokinetics of spirapril was unchanged in patients with different types of liver disease, including cirrhosis. However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients.
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  • 57
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    European journal of clinical pharmacology 40 (1991), S. 593-597 
    ISSN: 1432-1041
    Keywords: Dopamine ; Newborns ; critically ill patients ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5–20 μg · kg−1 · min−1, for presumed or proven sepsis and hypotensive shock. Steady-state concentrations of dopamine ranged from 0.013–0.3 μg/ml. Total body clearance averaged 115 ml · kg−1 · min−1. The apparent volume of distribution and elimination half life averaged 1.8 1 · kg−1 and 6.9 min, respectively. No relationship was observed between dopamine pharmacokinetics and gestational age, postnatal age or birthweight. Substantial interindividual variation was seen in dopamine pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate. Marked variation in clearance explains in part, the wide dose requirements of dopamine needed to elicit clinical response in critically ill newborn infants.
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  • 58
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    European journal of clinical pharmacology 40 (1991), S. 619-624 
    ISSN: 1432-1041
    Keywords: Inulin ; pharmacokinetics ; half life ; distribution ; concentration-dependent clearance ; healthy subjects ; chronic renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of inulin was studied in 30 healthy male and 10 healthy female volunteers, and 10 patients with stable chronic renal failure (mean creatinine clearance 45 ml·min−1) following intravenous infusion of 70 mg·kg−1 over 5 min. Plasma concentrations fell rapidly initially but the rate of decline decreased continuously over 8 h and a linear terminal elimination phase could not be identified. Inulin was excreted rapidly by the subjects with normal renal function and 97.3% of the dose was recovered in the urine in 8 h. There was a progressive highly significant fall in the renal clearance of inulin after 2 h as plasma concentrations fell below about 150 mg·l−1. Six to 8 h after administration the clearance was less than 50% of the initial value in the healthy volunteers and the corresponding fall in the renal patients was 33%. The concentration-dependent renal clearance of inulin was confirmed in “step-up” and “step-down” constant infusion studies in which clearances were measured at mean plasma concentrations ranging from 35.2 to 186.7 mg·l−1. These studies virtually excluded time, changes in posture and urine flow rate as important factors. There was no statistically significant fall in clearance during the first 2 h and kinetic analysis was based on data obtained over this time. Under these conditions the mean plasma half life, volume of distribution (Vss) and total body clearance of inulin in the healthy males, healthy females and patients with chronic renal failure were 73.2, 65.5 and 172.4 min, 10.5, 9.6 and 8.81·70 kg−1 and 113.3, 111.5 and 43.3 ml·min−1·70 kg−1 respectively. There were no sex differences in any of the kinetic variables. The mechanism of the concentration-dependent clearance of inulin is unknown but the findings are consistent with saturable renal tubular reabsorption. Care is required with the use of inulin for measurement of the glomerular filtration rate by the single injection technique.
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  • 59
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    European journal of clinical pharmacology 40 (1991), S. 631-633 
    ISSN: 1432-1041
    Keywords: Mefloquine ; ampicillin ; Thai subjects ; pharmacokinetics ; enterohepatic recycling ; drug interaction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a single oral dose of mefloquine given either alone or with ampicillin has been studied in 8 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with ampicillin (1648 vs 1228 ng·ml−1), as well as a significantly reduced terminal half life (15.3 vs 17.7 days), mean residence time (20.1 vs 23.4 days) and volume of distribution at steady state (14.1 vs 19.4 l·kg−1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 5 days was significantly increased by ampicillin (4.86 vs 3.27 μg·ml−1 day). These changes in mefloquine disposition after antibiotic treatment may be due both to an increase in fractional bioavailability and a reduction in the enterohepatic recycling of mefloquine.
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    European journal of clinical pharmacology 40 (1991), S. 637-638 
    ISSN: 1432-1041
    Keywords: Roxatidine acetate ; sucraflate ; pharmacokinetics
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    European journal of clinical pharmacology 45 (1993), S. 357-361 
    ISSN: 1432-1041
    Keywords: Circadian rhythms ; Indomethacin ; Ketoprofen ; pharmacokinetics ; time-varying models ; nonsteroidal anti-inflammatory drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A one-compartment model with first-order absorption has provided good fits to five sets of indomethacin data and four sets of ketoprofen data taken at different times of day. There was substantial variation in the model parameters with time of administration and most of the features of this variation applied equally to both drugs. From the data examined, the source of variation appears to be mainly in the absorption phase and this was confirmed using a chronokinetic analysis, in which simultaneous fits were obtained with time-variant rate parameters. However, there may also be circadian variation in protein binding. The danger of quoting parameter values for either of these two drugs based on administration at a single time of day has been illustrated, and this may well be true for other drugs.
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  • 62
    ISSN: 1432-1041
    Keywords: Gamma-hydroxybutyric acid ; pharmacokinetics ; dose-proportionality
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate withdrawal syndromes. Its absorption and disposition kinetics have been studied in 8 healthy male volunteers following oral administration of single doses of 12.5, 25 and 50 mg kg−1. The AUC increased disproportionately with the dose and so the apparent oral clearance decreased significantly as the dose was increased, whereas the terminal half-life and mean residence time increased. The peak plasma concentrations normalised to the lowest dose fell significantly with increasing doses, whilst the corresponding peak times increased. These findings suggest that both the oral absorption and the elimination of GHB are capacity-limited processes. GHB did not bind to significant extent to plasma proteins over the therapeutic concentration range. The pharmacokinetic parameters in healthy volunteers were not significantly different from those previously observed in alcohol-dependent patients with compensated alcoholic liver disease.
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  • 63
    ISSN: 1432-1041
    Keywords: Glyceryl trinitrate spray ; pharmacokinetics ; a/b-ratio ; pulmonary artery diastolic pressure ; finger pulse curve ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course and the magnitude of the effect of glyceryl trinitrate (GTN) on central venous (pulmonary artery diastolic pressure-PAPd) and peripheral arterial (a/b-ratio of the finger pulse wave) haemodynamics were compared in a randomized double-blind cross-over study in 12 patients suffering from congestive heart failure (NYHA II–III) with elevated PADd at rest (≥15 mm Hg). The data were obtained in a bioavailability study of two sprays of glyceryl trinitrate, which differed in their galenical characteristics and in the dose of GTN (0.4 mg vs. 0.8 mg). Following sublingual administration of each spray, PAPd, a/b-ratio and the plasma concentrations of GTN and its metabolites were measured up to 30 min. The relative bioavailability of GTN of the test preparation was estimated to be 157%, 161% and 147%, when calculated from the plasma concentration-time data or the integrated effect of GTN on a/b-ratio or PAPd, respectively. The mean time courses of the decrease in PAPd and the increase in the a/b-ratio of the finger pulse curve were mirror images. Thus, there was a strong correlation between the mean values of PAPd and a/b-ratio following the administration of glyceryl trinitrate. Since the slope of the relationship differed considerably between the patients, the magnitude of effect of GTN on PAPd in the individual patient could not be predicted from the changes in a/b-ratio.
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  • 64
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    European journal of clinical pharmacology 44 (1993), S. 463-466 
    ISSN: 1432-1041
    Keywords: Benazepril ; Proteinuria ; benazeprilat ; ACE inhibitor ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have investigated whether the pharmacokinetics and pharmacodynamics of the ACE inhibitor benazepril hydrochloride are altered with proteinuria by studying 8 patients with major proteinuria of different causes who were given a single dose of 10 mg p.o. The maximum plasma concentration of benazepril was found between 0.5 and 2 h after dosing (median 1 h). Its elimination was almost complete within 6 h. Peak plasma levels of benazeprilat, the active metabolite of benazepril, were observed between 1 and 6 h (median 2.5 h). The elimination of benazeprilat from plasma was biphasic, with mean initial and terminal half-lives of 3.0 and 17.3 h, respectively. On average, the pharmacokinetic parameters of benazepril and benazeprilat in the patients did not differ from those in a historical control group of healthy volunteers, but intersubject variability in the AUC and half-lives of benazeprilat was greater in the patients. Plasma ACE was completely inhibited from 1.5 to 6 h after dosing, and at 48 h the mean inhibition was still 42 %. Plasma renin showed substantial intersubject variation. Mean supine blood pressure (systolic/diastolic) was reduced from baseline by a maximum of 18/13 mm Hg at 6 h. Proteinuria was diminished after benazepril in 7 patients. In conclusion, the results of this study suggest that proteinuria in the nephrotic range does not require a change in benazepril dosage.
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  • 65
    ISSN: 1432-1041
    Keywords: dDAVP ; bioavailability ; gastrointestinal tract ; healthy volunteers ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP) from different regions of the gastrointestinal (GI) tract (stomach, duodenum, jejunum, ileum, colon, rectum) has been studied in 6 healthy, male volunteers aged 24 to 35 years, followed for 12 h after each drug administration. For i. v. administration the subjects received 4 μg dDAVP. For intestinal administration 400 μg dDAVP was directly applied to six distinct sites in the GI tract via two or four channel tubes with or without a distal occlusive balloon. Biological effects were assessed and plasma and urinary levels of dDAVP were measured using a specific, sensitive RIA. Urine osmolality remained elevated and diuresis decreased for 12 h following dDAVP administration irrespective of the site of application. After i. v. administration, the half-life of elimination of dDAVP was 60.0 min, plasma clearance 1.7 ml·min−1·kg−1, amount excreted in urine 2.0 μg and renal clearance was 0.8 ml·min−1·kg−1. The mean bioavailability (f) after gastric application was 0.19% (range 0.02–0.35%). f was 0.24% after duodenal application (range 0.04–0.62%), 0.19% after jejunal (range 0.01–0.41%), 0.03% after distal ileal (range 0.01–0.08%), 0.04% after proximal colonic (range 0.01–0.12%) and 0.04% after rectal (0.01–0.10%) application. The bioavailability was significantly higher in the three upper GI regions in comparison to the three lower regions. The bioavailability of dDAVP after gastric, duodenal and jejunal application was similar to that after swallowing a tablet in a previous study. Absorption from the ileum was lower than expected and no preferential site of absorption was found.
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  • 66
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    European journal of clinical pharmacology 42 (1992), S. 171-174 
    ISSN: 1432-1041
    Keywords: Quinine ; Malaria ; pharmacokinetics ; red blood cells ; plasma ; saliva ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quinine has been studied in ten healthy adult Africans after intravenous infusion and oral ingestion of a 500 mg dose. Blood and saliva samples were collected over 48 h and quinine in plasma, red cells and saliva was determined by HPLC. Quinine was rapidly and almost completely absorbed after an oral dose, with absorption half-life of 0.53 h, a tmax of 1–3 h and a bioavailability of 88%. Analysis of the i. v. data gave an apparent volume of distribution of 3.6 1·kg−1 and a plasma clearance of 0.19 l·kg−1·h−1. The concentration-time curves for plasma, red cells and saliva had declining phases were approximately parallel, giving a similar half-life that in all three media. The half-lives after the i. v. infusion also did not different from those after oral administration. The dose was well tolerated by both methods of administration.
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  • 67
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    European journal of clinical pharmacology 42 (1992), S. 175-179 
    ISSN: 1432-1041
    Keywords: 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) ; Triflusal ; triflusal metabolite (HTB) ; pharmacokinetics ; protein binding ; ultrafiltration ; binding constant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) is the main active metabolite of the platelet anti-aggregant drug triflusal. Its binding to plasma proteins of rats and healthy volunteers in vitro and in vivo has been studied. Rats were given a single oral dose of 50 mg·kg−1 triflusal and the healthy volunteers received 300 mg as a single oral dose or a multiple dose regimen of 600 mg every 24 h and 300 mg every 8 h, both for 13 days. Protein-free HTB was obtained by ultrafiltration. Unbound and total HTB concentrations were determined by HPLC. HTB was primarily bound to albumin in plasma. The Scatchard plots suggested two types of binding sites for HTB on the albumin molecule. In rats, the binding constants (K=intrinsic affinity constant, n=number of binding sites) were K1=1.4×105 l·mol−1, n1=1.23, and K2=4.1×103 l·mol−1 and n2=3.77. The mean plasma concentration in rats after oral administration was 185 (37) μg·ml−1 (protein-free HTB: 2.44 (0.77)%). The binding constants in human plasma were K1=4.7×105 l·mol−1, n1=1.93, K2=4.3 l·mol−1 and n2=4.28. The plasma HTB concentration in man (n=8) was 35 μg·ml−1 (Cmax) after a single oral dose of triflusal 300 mg, 172.96 μg·ml−1 (Cmax·ss) during the multiple dosage regimen of 300 mg every 8 h, and 131 μg·ml−1 (Cmax·ss) during the multiple oral dose regimen of 600 mg every 24 h. Unbound HTB ranged from 0.27 to 0.43%, depending on dose. HTB had high affinity for plasma albumin, which was not saturable after therapeutic doses. It showed linear elimination.
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  • 68
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    European journal of clinical pharmacology 42 (1992), S. 181-185 
    ISSN: 1432-1041
    Keywords: Glycerol ; brain oedema ; serum ; cerebrospinal fluid ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Glycerol 50 g infused i. v. over 2 to 6 h is widely used to treat cerebral oedema in patients with acute stroke. Its transit through the blood-cerebrospinal fluid barrier in subjects with uninflamed meninges has now been examined. In 7 patients with an external ventriculostomy for occlusive hydrocephalus, each of whom was given 500 ml of a 10% solution IV over 4 h, serum and CSF were repeatedly sampled during and after the infusion and glycerol was measured enzymatically. The highest serum glycerol level of 191–923 mg/l was observed at the end of the infusion. The maximum CSF glycerol of 18.7–110.8 mg/l was attained 0–1 h after the end of the infusion. Elimination both from serum and CSF approximated a single-exponential decay; the elimination half-life from serum was 0.29–0.56 h compared to 1.03–3.68 h from CSF. In six of the seven cases there was a temporary reversal of the serum/CSF concentration gradient during glycerol elimination. The ratios of the AUCs of CSF and serum, which describe the overall penetration of glycerol into CSF, ranged from 0.09–0.31. In conclusion, the serum level of glycerol produced by giving 50 g IV glycerol over 4 h may not be sufficiently high reliably dehydrate to brain tissue in many patients, and the slow elimination of glycerol from the CSF may be related to the so-called rebound phenomenon.
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  • 69
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    European journal of clinical pharmacology 42 (1992), S. 187-191 
    ISSN: 1432-1041
    Keywords: Dipyrone ; Acetylation phenotype ; metabolism ; pharmacokinetics ; urinary excretion ; metabolite clearance
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The formation and urinary excretion of the dipyrone metabolites, methylaminoantipyrine (MAA), aminoantipyrine (AA), formylaminoantipyrine (FAA) and acetylaminoantipyrine (AAA) were determined following administration of a single oral 1.0 g dose of dipyrone to 12 healthy volunteers. The AAA/AA plasma ratio showed that 3 subjects were slow and 9 were rapid acetylators. Pharmacokinetic parameters were determined separately for each group. A good correlation was found between the plasma and urine AAA/AA ratios. The renal clearance of the four metabolites was similar for both phenotypes. A significant difference in the rate of formation of dipyrone metabolites was found for AA, 0.25 (slow) vs 0.1 ml·min−1·kg−1 (rapid), and for AAA 0.75 (slow) vs 7.53 ml·min−1·kg−1 (rapid). There were comparable differences between slow and rapid acetylators in the AUC and the urinary excretion extrapolated to infinity for AA and AAA. The present results show that the kinetics of dipyrone metabolites in plasma and urine can provide a useful measure of the activity of the enzymes involved in their production.
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  • 70
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    European journal of clinical pharmacology 42 (1992), S. 197-201 
    ISSN: 1432-1041
    Keywords: Digoxin ; Salbutamol ; serum ; skeletal muscle digoxin ; pharmacokinetics ; drug interaction ; serum potassium
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of the β2-adrenoceptor agonist salbutamol has previously been shown to decrease serum digoxin concentration in healthy volunteers. A possible explanation of the phenomenon is a β2-adrenoceptor-mediated increase in the specific binding of digoxin to skeletal muscle. The present study was undertaken to further elucidate the effect of salbutamol on the pharmacokinetics of digoxin in man. Nine volunteers were studied on two occasions during salbutamol or placebo treatment. On test days salbutamol, 4 μg·kg−1·h−1 or saline was infused for 10 h, preceded and followed by four and three days, respectively, of oral administration. A single i. v. injection of digoxin 15 μg·kg−1, was given 20 min after starting the infusion. At the end of the infusion a muscle biopsy was taken from the vastus lateralis. Blood samples for the analysis of serum digoxin and potassium were repeatedly taken over 72 h. Urine was collected over a period of 24 h for determination of the renal excretion of digoxin and potassium. The serum digoxin concentration, expressed as the AUC 0–6 h was 15% lower during salbutamol infusion than during saline infusion. Salbutamol caused significantly faster elimination of digoxin from the central volume of distribution to deeper compartments. Salbutamol had no effect on the renal clearance of digoxin. The skeletal muscle digoxin concentration tended to be higher (48%) during salbutamol compared to placebo treatment. The serum potassium concentration was significantly lower after salbutamol compared to placebo, as was the rate of renal excretion of potassium. The results support the hypothesis that the salbutamol-induced decrease in serum digoxin is caused by increased distribution of digoxin to skeletal muscle (and possibly other tissues), and that this may be secondary to a β2-adrenoceptor-mediated increase in Na-K-ATPase activity.
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  • 71
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    European journal of clinical pharmacology 42 (1992), S. 203-207 
    ISSN: 1432-1041
    Keywords: Nicorandil ; pharmacokinetics ; angina pectoris ; uraemia ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of oral nicorandil 20 mg 12 hourly for 9 doses was evaluated in 21 hospitalized patients with angina pectoris due to coronary heart disease and with normal and impaired renal function. Patients were divided into 3 groups based on creatinine clearance (CLCr): GROUP I (n=6) 〉 80 ml/min, GROUP II (n=8) 20–80 ml/min, and GROUP III (n=7) 〈 20 ml/min. After the first dose, the total clearance of nicorandil (CL) value did not change with increasing renal failure and so was not dependent on creatinine clearance. After the last dose CL was 51 l·h−1 in Group I, 44 l·h−1 in Group II and 56 l·h−1 in Group III, and it was not related to creatinine clearance. The percentage of the dose excreted in the urine was 0.4%. No significant difference was noted in any of the other pharmacokinetic parameters examined in the three groups, not even on comparing values obtained on the first and last days of treatment. The findings suggest that there is no need to change the dose of nicorandil in subjects with different degrees of renal failure.
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  • 72
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    European journal of clinical pharmacology 46 (1994), S. 83-85 
    ISSN: 1432-1041
    Keywords: Enuresis ; Oxybutynine chloride ; children ; pharmacokinetics ; adverse effects ; anticholinergic actions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Anticholinergic adverse-effects in children treated with conventional doses of oxybutynine led us to measure plasma oxybutynine levels in children. 18 children, aged 5 to 13 y, who required treatment with oxybutynine chloride for daytime incontinence were studied. Plasma concentrations were measured on the fifth day of a course of treatment in which the dose was adapted to the child's body weight; the dose was given twice daily at 12-hour intervals. In 10 children aged between 5 and 8 y, the mean dose was 0.1 mg · kg−1. In 8 children aged between 10 and 13 years, the mean dose was 0.15 mg · kg−1. The highest concentration was usually found between 1 and 2 h after administration. The subsequent fall in concentration was rapid and after 6 h oxybutynine was no longer measurable in 14 of the children. The concentrations found were not different from those seen in adults given equivalent doses. The results show that plasma concentrations in children were not very different from those observed in adults if the dose were adapted to the body weight of the children. No special differences in paediatric use were revealed that might explain the particular adverse-effects. The results of the study argue against the dosage regimen proposed before these adverse events were detected. They strongly favour a dose adapted to the body weight of the child, with a 12-hour interval between doses.
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  • 73
    ISSN: 1432-1041
    Keywords: Steroid 5α-reductase inhibitor ; Testosterone metabolism ; MK-0434 ; pharmacodynamics ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A four-period, two-panel, single-rising-dose study (0.1–100 mg) was conducted in healthy males to investigate the pharmacodynamics, tolerability and pharmacokinetics of MK-0434, a steroid 5α-reductase inhibitor. MK-0434 was associated with a significant reduction in dihydrotestosterone, which was maximal at 24 h and maintained through 48 h post treatment. The maximum reduction was approximately 50 % and occurred at all doses above 5 mg (10, 25, 50 and 100 mg). MK-0434 appeared to have no effect on serum testosterone at these single doses. Rising single doses of MK-0434 were associated with an increase in Cmax and AUC but the changes were less than proportional to dose, most likely due to nonlinear absorption. MK-0434 given in single doses up to 100 mg was without significant adverse effects in healthy male volunteers. In summary, MK-0434 is a well-tolerated, potent, orally active 5α-reductase inhibitor in man.
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  • 74
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    European journal of clinical pharmacology 46 (1994), S. 261-265 
    ISSN: 1432-1041
    Keywords: Cystic fibrosis ; Cyclosporin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Cyclosporin (CsA) is currently the main immunosuppressive agent used in organ transplantation with considerable improvement in graft survival. Oral CsA solution is highly lipophilic, and its bioavailability may be reduced in cystic fibrosis (CF) heart-lung transplant recipients with pancreatic, gastrointestinal, and hepatic insufficiency. The bioavailability of oral CsA solution in 7 CF transplant recipients (5 male and 2 female with a mean age of 27 years and a mean weight of 49 kg) and 3 non-CF heart-lung recipients (1 male and 2 female with a mean age of 41 years and a mean weight of 60 kg) was studied. Following intravenous CsA administration, the kinetic curves were similar with no significant difference in the volume of distribution and clearance of CsA demonstrated between the CF and non-CF groups. The mean daily dose of oral CsA in 7 CF subjects (23.3 mg·kg−1) was significantly higher than the 3 non-CF heart-lung recipients (4.8 mg·kg−1). The mean maximum blood concentration of CsA for the oral dose was 776 ng·ml−1 for the 7 CF subjects, which was comparable with the mean peak values of 789 ng·ml−1 for the 3 non-CF control subjects. Poor enteral absorption of CsA probably accounts for the significantly lower mean bioavailability in the 7 CF subjects (14.9%) compared with the 3 non-CF control subjects (39.4%). The effects on the bioavailability of oral CsA solution by pancreatic enzymes (Creon) and histamine-2 antagonist (ranitidine) were also evaluated in the 7 CF subjects. No significant difference was demonstrated.
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  • 75
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    European journal of clinical pharmacology 44 (1993), S. 247-251 
    ISSN: 1432-1041
    Keywords: Proguanil ; Pregnancy ; Malaria ; cycloguanil ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and whole blood concentrations of proguanil, its active metabolite cycloguanil, and the inactive metabolite 4-chlorophenyl-biguanide, were measured by HPLC in 10 healthy Karen women in the last trimester of pregnancy, following a 200 mg single oral dose of proguanil. Four of these women were restudied 2 months after delivery. The pharmacokinetic properties of proguanil were similar during and after pregnancy. Median peak plasma concentrations of proguanil during pregnancy and following delivery were 212 and 215 ng·ml−1, and occurred at 4.5 and 5 h, respectively. Mean plasma AUC values for proguanil during and following pregnancy were 94 and 98 ng·h·ml−1·kg−1, respectively. Corresponding whole blood AUC values were 361 and 396 ng·h·ml−1·kg−1. The mean elimination half lives and mean residence times of proguanil in plasma and whole blood were 12.3 and 19.6 h and 13.8 and 20.7 h respectively during pregnancy. Following pregnancy these values were 17.1 and 19.7 h for plasma and 19.7 h and 20.2 h for whole blood respectively. Mean peak plasma and whole blood concentrations of cycloguanil following pregnancy were 25 and 22 ng·ml−1 respectively. During pregnancy peak cycloguanil concentrations in both plasma and whole blood were markedly lower, 13 and 12 ng ml−1, respectively. Two pregnant women (neither of whom were restudied) were probably poor metabolisers of proguanil. The mean ratio of proguanil to cycloguanil plasma AUC was 16.7 in the third trimester of pregnancy and 7.8 following pregnancy, compared with less than 5 in previously reported studies. The concentrations of 4-chlorophenylbiguanide in both plasma and whole blood in pregnant subjects were also lower than those after pregnancy. These data show that blood concentrations of the active antimalarial metabolite cycloguanil are reduced in late pregnancy and that the currently recommended dose of proguanil could be inadequate for antimalarial prophylaxis in pregnant women.
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  • 76
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    European journal of clinical pharmacology 44 (1993), S. 265-269 
    ISSN: 1432-1041
    Keywords: Cyclosporine ; Renal transplantation ; pharmacokinetics ; intraindividual variation ; circadian variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The intraindividual variability and circadian variation of oral cyclosporine (CsA) pharmacokinetics were studied over 24 h in 18 renal transplant recipients at steady state, and in 10 of the patients during a second 24 h period. The absolute percentage intraindividual difference in daytime AUC (0–12 h) ranged from 2% to 54% (mean 30%), and the corresponding variability in nighttime AUC (0–12 h) ranged from 5% to 80% (mean 34%). The pharmacokinetic variables t1/2, tmax and Cmax were more variable than the AUC (0–12 h) both during the day and at night. The evening trough level was significantly lower than the morning trough level; 185 ng · ml−1 versus 223 ng · ml−1. This, together with a significantly longer t1/2 in the night than the day, suggested circadian variability in the pharmacokinetics of CsA. In a separate retrospective study in 162 renal transplant recipients given CsA by constant intravenous infusion, repeated CsA blood concentration measurements at steady state showed lower concentrations during the day than the night, suggesting higher CsA clearance during daytime. It is concluded that CsA pharmacokinetics in renal transplant recipients, besides the well-known interindividual variability, also displays large intraindividual variability as well as circadian variation. Our findings further emphasize the necessity and difficulty of pharmacological monitoring in the clinical use of CsA in organ transplantation.
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  • 77
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    European journal of clinical pharmacology 44 (1993), S. 301-302 
    ISSN: 1432-1041
    Keywords: Adriamycin ; Haemodialysis ; adriamycinol ; pharmacokinetics ; moment analysis
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  • 78
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    European journal of clinical pharmacology 44 (1993), S. 305-306 
    ISSN: 1432-1041
    Keywords: Atenolol ; bioavailability ; intestinal absorption ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We investigated the dose proportionality after the intake of oral atenolol 25, 50, 100 and 150 mg. Standard tablets were taken by 8 healthy volunteers in randomised order of doses. The area under the curve divided by dose did not differ between the doses, indicating that the absorption of this hydrophilic compound, with known incomplete bioavailability, was constant over the range tested.
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  • 79
    ISSN: 1432-1041
    Keywords: Esmolol ; β1-Adrenoceptor antagonist ; tricresylphosphate ; pharmacokinetics ; effect kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of esmolol at different rates of infusion (100, 250 and 500 μg·kg−1 BW·min−1) were compared with β-adrenoceptor occupancy (β1 and β2, estimated by a subtype selective radioreceptor assay) and plasma concentrations of esmolol and its acid metabolite were measured by HPLC. Up to a rate of infusion of esmolol of 500 μg·kg−1 BW·min−1 there was a maximal β1-receptor occupancy of 84.7% while β2-receptor occupancy was below the detection limit; confirming the β1 selectivity of esmolol. Exercise-induced increases in heart rate and systolic blood pressure were reduced by esmolol in a dose-dependent manner. The estimated EC50 values of rate of infusion for the reduction in heart rate and systolic blood pressure during exercise were 113 and 134 μg·kg−1 BW · min−1, respectively. Additionally, heart rate and systolic blood pressure were reduced moderately at rest. Because of the short elimination half-life of esmolol caused by the rapid hydrolysis to its acid metabolite, 45 min after end of infusion high plasma concentrations of the metabolite (maximally 80 μg·ml−1) but no esmolol were detectable. Since no in vivo effects have been observed, despite the presence of high plasma concentrations of the metabolite, the metabolite did not participate in the observed effects up to an infusion rate of esmolol of 500 μg·kg−1 BW·min−1. The plasma concentrations of antagonist detected by radioreceptor assay and plasma concentrations of esmolol detected by HPLC showed a good correlation (r=0.97). Since the cardiovascular effects, determined before and 45 min after termination of infusion of esmolol were similar, it can be concluded that the observed effects on heart rate and systolic blood pressure are exclusively mediated by esmolol.
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  • 80
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    European journal of clinical pharmacology 49 (1996), S. 387-391 
    ISSN: 1432-1041
    Keywords: Key words Liver function tests; elderly ; pharmacokinetics ; geriatrics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66–92 y) and 12 healthy volunteers (20–35 y). Methods: Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance). Results: In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 μmol*h⋅l−1, clearance was reduced (5.0 vs. 11.8 l⋅h−1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P 〈 0.0001). Conclusion: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.
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  • 81
    ISSN: 1432-1041
    Keywords: Ramipril ; Piretanide ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and pharmacodynamics of single oral doses of 5 mg ramipril and 6 mg piretanide administered separately and in combination were determined in a single blind, randomised, 3-period cross-over study in 24 healthy male volunteers. The peak plasma concentrations of ramipril and ramiprilat increased slightly (from 11.9 to 14.8 ng/ml, and from 6.39 to 8.96 ng/ml, respectively) as did the area under the plasma concentration-time curve of ramipril (0–4 h) and ramiprilat (0–24 h) (from 15.8 to 19.8 ng·ml−1·h, and from 63.4 to 74.6 ng·ml−1·h, respectively). The urinary excretion of ramiprilat also rose (from 6.82 to 7.73 % of dose) following simultaneous treatment with piretanide. These effects were probably due to reduced first-pass metabolism of ramipril/ramiprilat to inactive metabolites. The blood pressure lowering effect, the time course of inhibition of ACE activity in plasma and the concentration-response relationship for the inhibition of plasma ACE activity were not affected by piretanide. The peak plasma concentration of piretanide was somewhat reduced (from 285 to 244 ng/ml) following simultaneous treatment with ramipril. No other pharmacokinetic parameter was affected. Piretanide increased urine flow, and sodium, chloride and potassium excretion, especially during the first 2 hours following administration. These pharmacodynamic parameters were not affected by ramipril. Thus, simultaneous administration of single oral doses of ramipril and piretanide caused modest changes in the peak and average plasma concentrations of both drugs, which did not lead to detectable alterations in the pharmacodynamic parameters measured in healthy volunteers.
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  • 82
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    European journal of clinical pharmacology 46 (1994), S. 573-574 
    ISSN: 1432-1041
    Keywords: Standard deviation ; Arithmetic mean ; pharmacokinetics
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  • 83
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    European journal of clinical pharmacology 46 (1994), S. 565-567 
    ISSN: 1432-1041
    Keywords: Phenytoin ; Saliva ; therapeutic drug monitoring ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of atropine-induced reductions in saliva flow rate on saliva phenytoin concentrations were evaluated in a randomised placebo-controlled crossover study in a group of epileptic patients stabilised on the drug. Pretreatment with atropine caused significant reductions in saliva flow rates during the first 4 h, compared to saline. The AUC0–4 h for saliva flow rate was significantly reduced by atropine (245 g vs 327 g) and the saliva phenytoin AUC0–4 h was significantly increased (5.6 μg · ml−1 · h vs 4.5 μg · ml−1 · h) without affecting plasma phenytoin concentrations. The saliva/plasma phenytoin AUC0–4 h ratio was therefore significantly increased by atropine (0.15 vs 0.12). However, there was a poor correlation between saliva/plasma phenytoin concentration ratios and saliva flow rates for the two treatments in the individual patients (correlation coefficient ranged from 0.25 to 0.65). These findings demonstrate that saliva phenytoin concentrations are increased by reductions in saliva flow rate. Caution is therefore required when saliva phenytoin concentrations are used for therapeutic monitoring in the presence of factors which may affect saliva flow rate.
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  • 84
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    European journal of clinical pharmacology 47 (1994), S. 61-65 
    ISSN: 1432-1041
    Keywords: Cyclosporine A ; kidney transplant ; nephrotic syndrome ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetic parameters of cyclosporine (CsA) were determined in 23 kidney transplant recipients and 19 children with nephrotic syndrome, after intravenous and oral administration. The mean bioavailability was 39 %, blood clearance was 0.55 l · h-1 · kg-1 and volume of distribution at steady-stade was 2.77 l · kg-1. The absorption profile was monophasic (67 %), biphasic (29 %) or poor (4 %). The maximum blood concentration of CsA was significantly higher in children with a monophasic profile than in children with a biphasic profile (550 vs 380 ng · ml-1). Blood clearance was significantly higher in the transplant recipients than in the patients with nephrotic syndrome (0.65 vs 0.43 l · h-1 · kg-1. Although age, haematocrit, creatinine clearance, serum albumin and cholesterol differed between the two groups, only haematocrit and creatinine clearance were significantly (negatively) correlated with CsA clearance.
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  • 85
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    European journal of clinical pharmacology 47 (1994), S. 81-84 
    ISSN: 1432-1041
    Keywords: Dihydrotachysterol ; bioavailability ; pharmacokinetics ; human ; HPLC
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The bioavailability of four preparations containing dihydrotachysterol (DHT2) was tested in two separate trials with administration of single, oral doses of 1 mg per individual. The relative bioavailability of corresponding preparations (capsules vs capsules and oral solution vs oral solution) was tested in a randomised, crossover pattern within the same group of volunteers. Two different groups of 24 healthy volunteers took part in each trial. Solution and capsule bioavailability was also compared inter-individually. A new sensitive HPLC-method (quantification limit 0.5 ng · ml-1) was used for the measurement of DHT2 concentration in serum. Three of the preparations tested had a similar bioavailability (mean AUC values of 195.5–223 ng · h · ml-1); the bioavailability of the fourth preparation (A.T.10 oral solution) was considerably lower (mean AUC value 111.5 ng · h · ml-1). The present dosage recommendations of all four preparations are identical. A new dosage recommendation is thus required for the oral solution with low bioavailability (A.T.10).
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  • 86
    ISSN: 1432-1041
    Keywords: Doxycycline ; bioavailability ; pH dependent absorption ; pharmacokinetics ; carrageenate ; adverse events
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of increased gastric pH (obtained by pre-treatment with omeprazole) on the bioavailability of doxycycline monohydrate and doxycycline carrageenate has been investigated in 24 healthy volunteers, using an open, randomised, four-treatment, four-period, crossover, 2×2 factorial design. Each subject received a single dose of 100 mg of each of the doxycycline formulations with and without pre-treatment with omeprazole (40 mg daily for 7 days). The two formulations were bioequivalent (rate and extent) during fasting without omeprazole pre-treatment, whereas after omeprazole, the monohydrate showed a highly significant decrease in bioavailability (38% for AUC and 45% for Cmax) compared to the carrageenate formulation, which was not affected by prior administration of omeprazole. Many of the subjects did not reach a therapeutic plasma level of doxycycline during the combination of omeprazole and doxycycline monohydrate, and most adverse events (mainly gastrointestinal) were reported after this combination. As large populations of patients have a high gastric pH due to frequent use of H2-blockers, proton pump inhibitors and antacids, as well as to physiological achlorhydria, the decreased absorption of doxycycline monohydrate may well have a clinical impact, for example when the patients are treated with tetracyclines for an infection.
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  • 87
    ISSN: 1432-1041
    Keywords: Medifoxamine ; pharmacokinetics ; pharmacodynamics ; elderly volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and psychomotor effects of medifoxamine, a 5 HT reuptake inhibitory antidepressant, were studied in healthy elderly volunteers after single and multiple dosing. The elimination half life (t1/2z) after single doses of 300 mg was 2.8 h — almost identical to that found in young volunteers. After seven days of dosing at 100 mg three times daily the mean corrected AUC after 300 mg significantly increased from 1.04 to 1.34 mg.h.l−1 and t1/2z increased to 4.0 h (NS). There were no significant changes in critical flicker fusion frequency, symbol digit substitution, continuous attention or choice reaction times.
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  • 88
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    European journal of clinical pharmacology 46 (1994), S. 179-180 
    ISSN: 1432-1041
    Keywords: Teicoplanin ; haemodialysis ; renal failure ; pharmacokinetics
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  • 89
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    European journal of clinical pharmacology 46 (1994), S. 237-242 
    ISSN: 1432-1041
    Keywords: Metoprolol ; bioavailability ; bioequivalence ; receptor binding assay ; pharmacokinetics ; sustained release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The bioavailability and pharmacodynamic bioequivalence of a conventional and an experimental sustained-release formulation of 100 mg metoprolol tartrate were studied in a randomised cross-over study in seven healthy volunteers by assessing over 24 h the plasma kinetics of R,S-metoprolol, its β1-adrenoceptor binding component, and by determining the extent to which the active drug moiety in plasma occupied rabbit lung β1-and rat reticulocyte β2-adrenoceptors. The formulations differed markedly in their kinetic characteristics: the peak plasma concentration (Cmax) of R,S-metoprolol after administration of the conventional formulation was 140 ng·ml−1, (n=7) and it was approximately one-third of that after the sustained-release formulation, 49 ng·ml−1, (n=6); the AUC0–24 h-values for the formulations were 700 and 310 ng·h·ml−1, respectively. The Cmax for the β1-adrenoceptor binding component of metoprolol was 180 ng·ml−1 (n=7) after administration of the conventional, and 74 ng·ml−1 after administration of the sustained-release formulation. The corresponding AUC0–24 h-values for the receptor binding component were 920 and 470 ng·h·ml−1 (n=7). Thus, the kinetic differences between R,S-metoprolol and the β1-receptor binding component were considerable and they were affected by the type of formulation. In general, after administration of the sustained-release formulation, the percentage β1- and β2-adrenoceptor occupancy of metoprolol in plasma was 5–15% less than after administration of the conventional formulation. At 0.5–1.5 h after drug intake the average β1-adrenoceptor occupancy of the conventional formulation varied between 80–90% and that of the sustained release formulation between 20–76%. At these times the differences in receptor occupancy were significant; at 0.5–2 h after drug intake the average β2-adrenoceptor occupancy of the conventional formulation varied from 20–30%, and that of the sustained-release formulation was 2–17%. At other times the difference in receptor occupancy between the formulations was not significant. The results demonstrate that plasma concentration-kinetics were more discriminating than β-adrenoceptor-binding in analysing bioequivalence. It was possible to determine the bioavailability of the active ingredient of metoprolol and to study pharmacodynamic bioequivalence by using receptor binding assays.
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  • 90
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    European journal of clinical pharmacology 47 (1995), S. 507-511 
    ISSN: 1432-1041
    Keywords: Methotrexate ; Juvenile rheumatoid arthritis ; pharmacokinetics ; age dependence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
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  • 91
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    European journal of clinical pharmacology 47 (1995), S. 525-530 
    ISSN: 1432-1041
    Keywords: Antipyrine disposition ; Obesity ; pharmacokinetics ; oxidative metabolism ; weight reduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
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  • 92
    ISSN: 1432-1041
    Keywords: Piroxicam ; β-Cyclodextrin ; pharmacokinetics ; healthy volunteers ; multiple dose ; adverse event
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
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  • 93
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    European journal of clinical pharmacology 46 (1994), S. 575-575 
    ISSN: 1432-1041
    Keywords: Renal clearance ; pharmacokinetics
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  • 94
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    European journal of clinical pharmacology 47 (1994), S. 75-79 
    ISSN: 1432-1041
    Keywords: Diltiazem ; Angina pectoris ; controlled release formulation ; metoprolol ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Diltiazem CR tablets 120 mg b.i.d. for 1 week were compared with plain tablets 60 mg q.i.d. in 13 healthy male volunteers in a study of pharmcokinetic variables. Their antianginal efficacy was also compared in 23 patients with stable angina pectoris who were already on metoprolol. Both studies were of randomised, cross over design, and the clinical study was double blind. The pharmacokinetic variables of the two formulations were very similar except for the longer tmax of 4.4 h for diltiazem CR in comparison to 2.9 h for the plain tablets. The mean relative bioavailability of diltiazem CR in comparison with plain tablets was 1.14. The clinical study showed that after four weeks on diltiazem CR 120 mg b.i.d. or diltiazem plain tablets 60 mg q.i.d. in addition to metoprolol, there were significant decreases in weekly anginal attacks from 11 to 5 attacks/week, the number of nitroglycerin tablets consumed from 6 to 3 tablets/week, and an increase in the maximum workload from 116 to 126 and 123 W for diltiazem CR and plain diltiazem tablets, respectively, as compared to placebo. Five of the patients were angina free during diltiazem treatment. No difference in antianginal efficacy between the two preparations was seen. It was concluded that CR 120 mg b.i.d. appears bioequivalent to plain diltiazem tablets 60 mg q.i.d.
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  • 95
    ISSN: 1432-1041
    Keywords: Oxcarbazepine ; 10,11-dihydro-10-hydroxy-carbamazepine ; renal impairment ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have studied the effect of renal impairment on the pharmacokinetics of oxcarbazepine, its active monohydroxy-metabolite (which predominates in plasma), their glucuronides, and the inactive dihydroxy-metabolite after a single oral dose of oxcarbazepine (300 mg). Six subjects with normal renal function and 20 patients with various degrees of renal impairment participated. The mean areas under the plasma concentration-time curves of oxcarbazepine and its monohydroxy-metabolite were 2–2.5-times higher in patients with severe renal impairment (CLCR〈10 ml·min−1) than in healthy subjects. The apparent elimination half-life of the monohydroxy-metabolite [19 (SD 3) h] in these patients was about twice that in healthy subjects. The effect of renal impairment on the plasma concentrations of glucuronides was more marked. The renal clearances of the unconjugated monohydroxy-metabolite and its glucuronides (the main compounds recovered in urine) correlated well with creatinine clearance. The maximum target dose in patients with slight renal impairment (CLCR〉30 ml·min−1) should not be changed. In patients with moderate renal impairment (CLCR10–30 ml·min−1) it should be reduced by 50%. In patients with severe renal impairment (CLCR〈10 ml·min−1), the glucuronides of oxcarbazepine and its monohydroxy-metabolite are likely to accumulate during repeated administration, and dosage adjustment of oxcarbazepine in these patients could not be proposed from this single administration study.
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  • 96
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    European journal of clinical pharmacology 48 (1995), S. 385-390 
    ISSN: 1432-1041
    Keywords: Furosemide ; Dialysis ; continuous ambulatory peritoneal ; drug disposition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
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  • 97
    ISSN: 1432-1041
    Keywords: Caffeine ; Cardio-green ; Indocyanine Green ; altitude ; metabolism ; pharmacokinetics ; hypoxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
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  • 98
    ISSN: 1432-1041
    Keywords: Diltiazem ; sustained-release formulation ; pharmacokinetics ; bioavailability ; bioequivalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
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  • 99
    ISSN: 1432-1041
    Keywords: Diabetes ; Human insulin ; Lorazepam ; pharmacokinetics ; glucuronidation ; enterohepatic circulation ; animal insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
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  • 100
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    European journal of clinical pharmacology 48 (1995), S. 273-277 
    ISSN: 1432-1041
    Keywords: Mesalamine ; 5-aminosalicylic acid ; controlled release capsules ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
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