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  • nitrogen  (320)
  • pharmacokinetics  (273)
  • fish  (211)
  • Springer  (803)
  • 2020-2023
  • 2005-2009
  • 1995-1999  (803)
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  • 1
    Electronic Resource
    Electronic Resource
    Human Interindividual Variability in Parameters Related to Health Risks (1999)
    Springer
    Risk analysis 19 (1999), S. 711-726 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007045922532
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  • 2
    Electronic Resource
    Electronic Resource
    Evaluation of the Uncertainty in an Oral Reference Dose for Methylmercury Due to Interindividual Variability in Pharmacokinetics (1999)
    Springer
    Risk analysis 19 (1999), S. 547-558 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007017116171
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  • 3
    Electronic Resource
    Electronic Resource
    The impact of nitrogen fertilization of tomato on feeding site selection and oviposition by Trialeurodes vaporariorum (1998)
    Springer
    Entomologia experimentalis et applicata 86 (1998), S. 175-182 
    Details
    ISSN: 1570-7458
    Keywords: Aleyrodidae ; greenhouse whitefly ; nitrogen ; host selection ; oviposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Tomato plants, Lycopersicon esculentum Miller cv 'Tres Cantos', were supplied with high (308 ppm), medium (140 ppm) and low (84 ppm) nitrogen doses in order to determine the influence of nitrogen fertilization on feeding and oviposition site selection by greenhouse whitefly adults, T. vaporariorum (Westwood). The nitrogen and water content was higher in plants supplied with 308 N ppm than in plants with medium or low nitrogen doses and no differences were found in soluble sugar content. The leaves of the upper plant stratum (leaves 1–5) had the greatest nitrogen and water content, independent of the nitrogen dose applied. The plants were exposed to T. vaporariorum adults into a greenhouse under two current (late autumn-winter and spring-early summer) situations of the tomato crop in the Mediterranean area. The distribution of whitefly adults on the plants was affected by the nitrogen dose in both experimental conditions, the number of adults was higher on the plants supplied with high nitrogen dose. Within plants, adult distribution was affected by leaf position, the upper plant stratum being preferred for feeding. Whitefly females selected for oviposition and laid more eggs on plants and leaves of plants with higher nitrogen and water contents. We conclude that whitefly host selection for feeding and ovipositing are related to differences in nitrogen and water content of the host plant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1003145813704
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  • 4
    Electronic Resource
    Electronic Resource
    Fecundity and egg distribution of the herbivore Spodoptera pectinicornis as influenced by quality of the floating aquatic plant Pistia stratiotes (1998)
    Springer
    Entomologia experimentalis et applicata 86 (1998), S. 295-304 
    Details
    ISSN: 1570-7458
    Keywords: fecundity ; host plant quality ; Pistia stratiotes ; Spodoptera pectinicornis ; nitrogen ; trichomes ; oviposition ; biological control of weeds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We determined the influence of larval host quality of the floating aquatic weed Pistia stratiotes L. (Araceae) on the fecundity and egg distribution of the biological control agent Spodoptera pectinicornis (Hampson) (Lepidoptera: Noctuidae). Different nutritional levels were produced by growing plants with relatively low and high levels of nitrogen, phosphorus and potassium fertilizer. Female and male pupal biomass were significantly greater when the larvae were fed leaves from the high fertilizer plants. Although the fertilizer treatments did not significantly influence total fecundity, there was an indirect effect as adults from larger pupae were more fecund. Regardless of treatment, ovipositing females formed a depression in the leaf surface by removing trichomes into which they deposited the egg masses. Most of the egg masses were laid on the lower leaf surface, on leaf positions 5–8 (counting from the young inner to the outer leaves) and during days 1–2 post-eclosion. Most of the eggs were laid in masses but about 12% were solitary. Females fed the low fertilizer treatment laid a greater proportion (mean ± s.e.) of their eggs as solitary eggs (17.3 ± 3.4% of total eggs) than did females fed the high fertilizer treatment (8.3 ± 2.3% of total eggs). The increased percentage of solitary eggs laid by the females from the low quality larval diet may be an adaptive response to decrease competition among the progeny.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1003193220069
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  • 5
    Electronic Resource
    Electronic Resource
    The effect of nitrogen fertilizer applied to Euphorbia pulcherrima on the parasitization of Bemisia argentifolii by the parasitoid Encarsia formosa (1996)
    Springer
    Entomologia experimentalis et applicata 78 (1996), S. 105-110 
    Details
    ISSN: 1570-7458
    Keywords: Bemisia argentifolii ; Encarsia formosa ; poinsettia ; parasitoids ; nitrogen ; tri-trophic level interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract More wasps of Encarsia formosa Gahan (Hymenoptera: Aphelinidae) were found on fertilized poinsettias, Euphorbia pulcherrima (Willd.) (Euphorbiaceae), than on non-fertilized plants. Parasitization of Bemisia argentifolii Bellows & Perring (Homoptera: Aleyrodidae) by E. formosa was higher on plants treated with calcium nitrate than with ammonium nitrate or on control plants. In a no-choice test, host feeding by E. formosa was higher when hosts were on fertilized plants than when hosts were on control plants. The nitrogen content of whitefly pupae reared on plants treated with ammonium nitrate was higher than those on calcium nitrate-treated plants. Variability in the parasitization of B. argentifolii by E. formosa appears to be due to host plant-mediated differences in the whiteflies. E. formosa may be influenced by the nutritional suitability of the host, which influences whether wasps continue to oviposit, feed, or disperse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00304461
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  • 6
    Electronic Resource
    Electronic Resource
    Plant growth stage effects on the feeding and growth responses of the bertha armyworm,Mamestra configurata to canola and mustard foliage (1995)
    Springer
    Entomologia experimentalis et applicata 74 (1995), S. 55-61 
    Details
    ISSN: 1570-7458
    Keywords: Brassica rapa ; B. juncea ; consumption rate ; glucosinolates ; growth rate ; indolyl ; isothiocyanate ; Mamestra configurata ; nitrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Mamestra configurata (Walker) (Lep., Noctuidae) larvae were fed excisedBrassica juncea (commercial brown mustard) orB. rapa cv. Tobin (Canola) foliage of three plant growth stages-rosette (stage 2), stem elongation (stage 3) and flowering (stage 4). Relative consumption rates (RCRi) were not significantly different between the plant species. Within theB. juncea treatments, there were no significant growth stage differences in RCRi. However, withinB. rapa, RCRi increased with advancing plant growth stage. Larvae fedB. juncea foliage had significantly reduced relative growth rates (RGRi) compared to larvae fedB. rapa foliage. Within theB. juncea treatments, RGRi decreased with advancing plant growth stage. There were no significant growth stage differences in RGRi in theB. rapa treatments. RGRi was inversely proportional to the levels of isothiocyanate-releasing glucosinolates in theB. juncea treatments. RCRi was inversely proportional to the levels of indolyl glucosinolates in theB. rapa treatments. Levels of total phenols and catechols inB. juncea did not show any trend which could be related to growth stage effects in the insect nutritional indices. InB. rapa, levels of phenols and catechols in stage 3 and 4 foliage were lower than that of stage 2 foliage. Analyses of total nitrogen in field-grown plants showed reductions in percent nitrogen from rosette to flowering stage foliage. The response ofM. configurata to different growth stages of its host plants are discussed in relation to changing levels of allelochemicals and nitrogen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02383167
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  • 7
    Electronic Resource
    Electronic Resource
    Compensatory responses of Samea multiplicalis larvae when fed leaves of different fertilization levels of the aquatic weed Pistia stratiotes (1999)
    Springer
    Entomologia experimentalis et applicata 92 (1999), S. 205-216 
    Details
    ISSN: 1570-7458
    Keywords: Samea multiplicalis ; Spodoptera pectinicornis ; Pistia stratiotes ; waterlettuce ; nitrogen utilization efficiency ; compensatory feeding ; nitrogen ; biological control of weeds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Compensatory responses of caterpillars fed low quality food include increased consumption and utilization of essential nutrients. Information about an insect's responses to nutritional challenges from their host plants could benefit weed biological control efforts in the selection and establishment of new agents. The target weed, Pistia stratiotes L. (Araceae) is a floating aquatic plant that has relatively low nitrogen levels which are further diluted with high water content. Efforts to establish the insect Spodoptera pectinicornis (Hampson) (Lepidoptera: Noctuidae) for biological control of P. stratiotes could benefit by examining the nutritional responses of a similar widely established lepidopteran species, Samea multiplicalis (Guenèe) (Lepidoptera: Pyralidae). Larvae of this species were fed leaves of P. stratiotes plants that had been fertilized (NPK) at high and low rates. The leaves of the fertilized plants had a 4.3-fold increase in nitrogen (dry weight) and a 1.6-fold increase in water content. The results suggest that no compensatory increases occurred in larvae fed leaves from the low fertilized plants as no changes were found in fresh mass consumption or nitrogen utilization efficiency. Consequently, development time from second-third instars to pupation was delayed about 3 days compared with larvae fed the high nitrogen leaves. Furthermore, consumption of nitrogen was only 30% and its accumulation into larval tissues was only 60% compared with the larvae fed the high fertilized leaves. The resulting larvae had both a final biomass and a growth rate that were reduced by 40%. Regardless of plant fertilizer level, the larvae fed at a rate 5–10 times greater than that of similar lepidopteran species consuming either low or high quality diets, suggesting that the S. multiplicalis larvae may be functioning at their biological limit for ingesting food.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1003771512722
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  • 8
    Electronic Resource
    Electronic Resource
    Comparative effect of short term exposures of Callosobruchus subinnotatus to carbon dioxide, nitrogen, or low temperature on behavior and fecundity (1998)
    Springer
    Entomologia experimentalis et applicata 89 (1998), S. 243-248 
    Details
    ISSN: 1570-7458
    Keywords: Coleoptera ; bruchidae ; anesthesia ; carbon dioxide ; nitrogen ; cold ; oviposition and mating
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The effect of anesthetizing with carbon dioxide, nitrogen, or low temperature on the reproductive behavior and fecundity of Callosobruchus subinnotatus was investigated. Males and females anesthetized with N2 as virgins had shorter recovery time, copulated earlier, and had shorter mating time than those subjected to CO2 or low temperature. Exposure of males and females to 2.0±0.5 °C for 10 min had the most profound effect on the recovery periods, copulation time, and duration of mating. Adults anesthetized with CO2 and low temperature laid fewer eggs than those anesthetized with N2. Females were more affected than males by the treatments, except when males were chilled for 10 min, and this prolonged the time for commencement of mating. The mode of anesthesia could affect egg production because vitellogenesis and choriogenesis take place in the imago stage of bruchids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1003503623654
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  • 9
    Electronic Resource
    Electronic Resource
    The effect of stem and cob borers on maize subjected to different nitrogen treatments (1995)
    Springer
    Entomologia experimentalis et applicata 77 (1995), S. 205-210 
    Details
    ISSN: 1570-7458
    Keywords: nitrogen ; maize ; lepidopterous stem and cob borers ; Sesamia calamistis ; Eldana saccharina ; Mussidia nigrivenella ; Cryptophlebia leucotreta ; dead hearts ; stem tunneling ; yields
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The influence of four nitrogen levels (0, 60, 90 and 120 kg N/ha) on growth of maize and development of lepidopterous pests was investigatdd in a field trial. Nitrogen had a positive effect on both plant growth variables (plant height, stem diameter and yield), and development and survival ofSesamia calamistis andEldana saccharina, and thereby increased the incidence of dead hearts and stem tunneling. However, the percent yield loss due to artificial infestation decreased with increasing N application rate from 20% to 11% in the in the 0kg/ha and 120kg/ha treatment, respectively. Using a multiple regression analysis, plant height, plant diameter and stem tunneling were found to be the most important variables explaining the variability in maize yield.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02383035
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  • 10
    Electronic Resource
    Electronic Resource
    Plant quality or quantity? Host exploitation strategies in three Chrysomelidae species associated with Asteraceae host plants (1999)
    Springer
    Entomologia experimentalis et applicata 92 (1999), S. 165-177 
    Details
    ISSN: 1570-7458
    Keywords: Chrysomelidae ; herbivory ; Asteraceae ; life history ; nitrogen ; plant quality ; season
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Phytophagous insects which feed on the leaves of herbaceous host plants have to adapt their life histories to the fact that protein nitrogen is usually highest in growing tissues in spring. We monitored field populations of larvae and adults of three chrysomelid species (Galeruca tanaceti (L.) (main host Achillea millefolium (L.) Yarrow), Cassida rubiginosa (Mueller) (main host Cirsium arvense (L.) Scop.) and Oreina luctuosa (Suffrian) (host Centaurea scabiosa (L.)) together with the amount of protein nitrogen of their food resources and host plant biomass. As expected, the development of host quality, measured as concentration of protein nitrogen, and host plant biomass showed inverse trends during the season. The euryphagous G. tanaceti attacks Achillea early and profits from high nitrogen concentrations in the leaves. Occasional overexploitations of local populations of Achillea are compensated by the capacity to move to other host species. In C. rubiginosa, a species with a host range restricted to the Cardueae, the main larval feeding activity is postponed to a period when the nitrogen content of the host leaves had dropped to 50% of its initial value, but when host plant biomass had increased by 30%. In the monophagous O. luctuosa the larval development is synchronized with a still later phase of host phenology, at which the nitrogen content is below 50% but plant biomass has reached its maximum. There seem to be selection factors, which oppose the use of high quality food in spring and which force the latter two species to postpone their larval development to a later time in the year. This could be caused by numerous factors like, for example, mean daytime temperature. Later in the season the larvae have to cope with the low quality of their host plants. They have, however, the advantage of large quantities of food available. A laboratory study with adults and mature larvae of O. luctuosa shows that this species can overcome low levels of protein nitrogen either by selecting younger leaves with higher nitrogen concentrations or by increasing the daily food consumption rate (RCR) on leaves with a low level of nitrogen and by a prolongation of the feeding period. In this way the larvae compensate the effect of lower daily growth rates (RGR) and a lower food conversion index (ECI) on poor food quality: Regardless of the level of protein nitrogen there was no statistically significant difference in total gain of weight during the third-instar feeding period and in the weight at the end of the third larval stage. The three investigated chrysomelids show that there exists a broad spectrum of adaptations to overcome the dilemma of variable food quality.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1003709622409
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  • 11
    Electronic Resource
    Electronic Resource
    Effects of cosolvents cetyltrimethylammonium bromide on the thresholds for nucleation of nitrogen in aqueous solutions (1995)
    Springer
    Journal of solution chemistry 24 (1995), S. 1059-1073 
    Details
    ISSN: 1572-8927
    Keywords: Supersaturation ; nitrogen ; cosolvent ; cetyltrimethylammonium bromide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The decomposition of ammonium nitrite in water creates a supersaturated solution of nitrogen. The same process occurs in water-organic solvent mixtures. Acetone, dioxane, dimethylsulfoxide (DMSO) and dimethylformamide (DMF) are the cosolvents used in this study. The limits of supersaturation of nitrogen (C SL /mol L−1) were determined in all of these solvent mixtures by releasing the dissolved gas sonicationally and measuring the volume of released gas. C SL was generally increased in the presence of cosolvents. The effectiveness sequence of organic solvents was found to be as DMF〈DMSO〈Dioxanet≅Acetone. Transportation period of small bubbles formed during sonication is changed by compositions of solvent mixtures. These periods may depend on the viscosity of the solution. Effects of the presence of cetyltrimethylammonium bromide were also studied. It was concluded that there may be a relation between the strength of the watercosolvent H-bonds and C SL and all of the measured quantities of this study were generally affected by micelle formation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00973522
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  • 12
    Electronic Resource
    Electronic Resource
    Open-Air Litter Foraging in the Nasute Termite Longipeditermes longipes (Isoptera: Termitidae) (1998)
    Springer
    Journal of insect behavior 11 (1998), S. 179-189 
    Details
    ISSN: 1572-8889
    Keywords: open-air foraging ; caste ; polyethism ; litter feeder ; nitrogen ; termite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The Southeast Asian nasute termite Longipeditermes longipes forages on the open ground on leaf litter. Its monomorphic workers carry back food balls in their mandibles while dimorphic soldiers defensively surround the marching columns and the foraging patches. When mechanically disturbed, workers hide under the litter, whereas antennating soldiers face as closely as possible the source of disturbance. Foragers prefer the lower, nitrogen-rich layer of the litter. Soldier behavior and column organization (returning workers in the center lanes, outgoing workers in the two flanking lanes) are similar to those in the related genera Hospitalitermes and Lacessititermes, which, however, tend to forage above ground.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1021039722402
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  • 13
    Electronic Resource
    Electronic Resource
    Simulation of kinetics of nitrogen desorption from Rh(111) (1996)
    Springer
    Catalysis letters 37 (1996), S. 163-165 
    Details
    ISSN: 1572-879X
    Keywords: nitrogen ; Rh(111) ; thermal desorption ; Arrhenius parameters ; lateral interactions ; NO decomposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Associative desorption of N atoms from the Rh(111) surface is simulated in the framework of the lattice-gas model. The Arrhenius parameters and nearest-neighbour lateral interaction employed to describe the measured thermal desorption spectra are as follows:v=1013 s−1,E d=40 kcal/mol, and ε1=1.7 kcal/mol. The results obtained are used to clarify the role of nitrogen desorption in the NO + CO reaction on Rh(111) atT=400–700 K andP NO≈P CO≈0.01 atm.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00807748
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  • 14
    Electronic Resource
    Electronic Resource
    The effect of chronic heat stress on cortisol levels in the antarctic fishPagothenia borchgrevinki (1995)
    Springer
    Cellular and molecular life sciences 51 (1995), S. 768-774 
    Details
    ISSN: 1420-9071
    Keywords: Cortisol ; stress ; heat ; Antarctic ; fish
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Radioimmunoassay was used to determine levels of the stress-inducible glucocorticoid, cortisol, circulating in the plasma of the extremely stenothermal Antarctic fishPagothenia borchgrevinki at rest and after heat stress. Fish sampled immediately after capture (−1.9°C) had low cortisol levels (10.4±1.4 ng ml−1, mean±SEM) as did fish which were laboratory rested for 3 days. Sudden exposure to 5°C (48h) resulted in a peak cortisol value after 3 h (69.9±6.8 ng ml−1) whereas exposure to 8°C (6h) resulted in a peak value after 1 h (73.5±8.0 ng ml−1). At both temperatures levels remained significantly elevated (p〈0.05) for the entire period of exposure. Increased temperature also resulted in a significant change in haemoglobin, haematocrit and mean cell haemoglobin concentration (MCHC) (p〈0.05). Plasma lactate was significantly elevated only after exposure to 8°C (p〈0.05). Plasma cortisol levels fromP. borchgrevinki are reported here for the first time and show this cryopelagic Antarctic species to have an unusual hormonal stress profile.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01922428
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  • 15
    Electronic Resource
    Electronic Resource
    FTIR spectroscopic evidence of formation of geminal dinitrogen species during the low-temperature N2 adsorption on NaY zeolites (1999)
    Springer
    Catalysis letters 58 (1999), S. 21-26 
    Details
    ISSN: 1572-879X
    Keywords: adsorption ; adsorption isotherms ; dinitrogen ; FTIR spectroscopy ; geminal species ; NaY ; nitrogen ; zeolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Adsorption of N2 on NaY zeolites at 85 K and equilibrium pressures higher than 1 kPa results in the formation of geminal dinitrogen complexes characterized by an IR band at 2333.5 cm−1 (2255.4 cm−1 after adsorption of 15N2). With decreasing equilibrium pressure the complexes tend to loose one N2 ligand, thus forming linear species characterized by an IR band at 2336.8 cm−1 (2258.7 cm−1 after adsorption of 15N2). All species disappear completely after evacuation. Co-adsorption of N2 and CO revealed that the dinitrogen complexes are formed on Na+ cations. The changes in the concentrations of the linear and geminal N2 species with the changes in the equilibrium pressure are excellently described by equations of adsorption isotherms proposed earlier for mono- and di-carbonyls.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1019040825491
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  • 16
    Electronic Resource
    Electronic Resource
    Pure and Binary Gas Adsorption Equilibria and Kinetics of Methane and Nitrogen on 4A Zeolite by Isotope Exchange Technique (1999)
    Springer
    Adsorption 5 (1999), S. 145-158 
    Details
    ISSN: 1572-8757
    Keywords: kinetics ; isotope-exchange ; nitrogen ; adsorption ; methane ; zeolite ; equilibria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Physics , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The Isotope Exchange Technique (IET) was used to simultaneously measure pure and binary gas adsorption equilibria and kinetics (self-diffusivities) of CH4 and N2 on pelletized 4A zeolite. The experiment was carried out isothermally without disturbing the adsorbed phase. CH4 was selectively adsorbed over N2 by the zeolite because of its higher polarizability. The multi-site Langmuir model described the pure gas and binary adsorption equilibria fairly well at three different temperatures. The selectivity of adsorption of CH4 over N2 increased with increasing pressure at constant gas phase composition and temperature. This curious behavior was caused by the differences in the sizes of the adsorbates. The diffusion of CH4 and N2 into the zeolite was an activated process and the Fickian diffusion model described the uptake of both pure gases and their mixtures. The self-diffusivity of N2 was an order of magnitude larger than that for CH4. The pure gas self-diffusivities for both components were constants over a large range of surface coverages (0 〈 θ 〈 0.5). The self-diffusivities of CH4 and N2 from their binary mixtures were not affected by the presence of each other, compared to their pure gas self-diffusivities at identical surface coverages.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008917308002
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  • 17
    Electronic Resource
    Electronic Resource
    Two kinds of adsorbed N atoms with different reactivities with H2 on a Pt0.25Rh0.75(100) surface (1998)
    Springer
    Catalysis letters 52 (1998), S. 151-155 
    Details
    ISSN: 1572-879X
    Keywords: platinum ; rhodium ; alloy ; surface composition ; nitrogen ; oxygen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Two kinds of adsorbed N atoms exist on a Pt0.25Rh0.75(100) surface. One desorbs at 490 K and the other desorbs at 650 K. The former reacts with H2 at 400 K, but the latter does not. It is supposed that the adsorption of these two N atoms is responsible of the surface composition, ratio of Pt and Rh.
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    URL: http://dx.doi.org/10.1023/A:1019000326574
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    Management-induced change in labile soil organic matter under continuous corn in eastern Canadian soils (1997)
    Springer
    Biology and fertility of soils 26 (1997), S. 88-94 
    Details
    ISSN: 1432-0789
    Keywords: Key words Microbial biomass C ; Water-soluble organic carbon ; Light fraction organic carbon ; Fertilizer ; nitrogen ; 13C nuclear magnetic resonance ; Infrared spectrophotometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Soil samples taken from four experimental sites that had been cropped to continuous corn for 3–11 years in Ontario and Quebec were analyzed to evaluate changes in quantity and quality of labile soil organic carbon under different nitrogen (N) fertility and tillage treatments. Addition of fertilizer N above soil test recommendations tended to decrease amounts of water-soluble organic carbon (WSOC) and microbial biomass carbon (MBC). The quality of the WSOC was characterized by 13C nuclear magnetic resonance and infrared spectrophotometry and the results indicated that carbohydrates, long-chain aliphatics and proteins were the major components of all extracts. Similar types of C were present in all of the soils, but an influence of management was evident. The quantity of soil MBC was positively related to the quantities of WSOC, carbohydrate C, and organic C, and negatively related to quantities of long-chain aliphatic C in the soil. The quantity of WSOC was positively related to the quantities of protein C, carbohydrate C, and negatively related to the quantity of carboxylic C. The quantity of soil MBC was not only related to quantities of soil WSOC but also to the quality of soil WSOC.
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    URL: http://dx.doi.org/10.1007/s003740050348
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    Nitrogen uptake and growth of two citrus rootstock seedlings in a sandy soil receiving different controlled-release fertilizer sources (1998)
    Springer
    Biology and fertility of soils 26 (1998), S. 169-172 
    Details
    ISSN: 1432-0789
    Keywords: Key words Urea ; Coated fertilizers ; Ammonium ; nitrogen ; Nitrate nitrogen ; Nitrogen uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Understanding the fate of different forms of nitrogen (N) fertilizers applied to soils is an important step in enhancing N use efficiency and minimizing N losses. The growth and N uptake of two citrus rootstocks, Swingle citrumelo (SC), and Cleopatra mandarin (CM), seedlings were evaluated in a pot experiment using a Candler fine sand (hyperthermic, uncoated, Typic Quartzipsamments) without N application or with 400 mg N kg–1 applied as urea or controlled-release fertilizers (CRF; either as Meister, Osmocote, or Poly-S). Meister and Osmocote are polyolefin resin-coated urea with longevity of N release for 270 days (at 25°C). Poly-S is a polymer and sulfur-coated urea with release duration considerably shorter than that of either Meister or Osmocote. The concentrations of 2 M KCl extractable nitrate nitrogen (NO3 –-N) and ammonium nitrogen (NH4 +-N) in the soil sampled 180 days and 300 days after planting were greater in the soil with SC than with CM rootstock seedlings. In most cases, the extractable NH4 + and NO3 – concentrations were greater for the Osmocote treatment compared to the other N sources. For the SC rootstock seedlings, dry weight was greater with Meister or Poly-S compared with either Osmocote or urea. At the end of the experiment, ranking of the various N sources, with respect to total N uptake by the seedlings, was: Meister = Osmocote 〉 Poly-S 〉 Urea 〉 no N for CM rootstock, and Meister = Poly-S = Osmocote 〉 Urea 〉 no N for SC rootstock. The study demonstrated that for a given rate of N application the total N uptake by seedlings was greater for the CRF compared to urea treatment. This suggests that various N losses were lower from the CRF source as compared to those from soluble fertilizers.
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    URL: http://dx.doi.org/10.1007/s003740050363
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    Microbial contribution to extractable N and P after air-drying of dry tropical soils (1997)
    Springer
    Biology and fertility of soils 26 (1997), S. 31-34 
    Details
    ISSN: 1432-0789
    Keywords: Key words Microbial biomass ; Air-drying ; Extractable ; nitrogen ; Extractable phosphorus ; Tropical soil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The microbial contribution to extractable N and P after the air-drying of eight Indian dry tropical Ultisols was quantified. Air-drying of the soils decreased microbial biomass C by 25–53% but increased extractable N and P by 14–34% and 24–121%, respectively. This increase in the extractable N and P was accounted for, to some extent, by microbial biomass killed due to air-drying. Microbial biomass contributes 17–36% and 19–82% to the extractable N and P, respectively, possibly due to air-drying of the soils. I conclude that due to contamination of microbial biomass with the available nutrients in air-dried soils, measurements of extractable nutrients should be made on field-moist soils.
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    URL: http://dx.doi.org/10.1007/s003740050339
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    Interspecific variation in sustained swimming ability of late pelagic stage reef fish from two families (Pomacentridae and Chaetodontidae) (1998)
    Springer
    Coral reefs 17 (1998), S. 111-119 
    Details
    ISSN: 1432-0975
    Keywords: Key words Dispersal ; coral reefs ; fish ; swimming ; Larvae ; Juveniles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences
    Notes: Abstract  Characteristics of the pelagic stages of reef fishes have generally been investigated at the family level, which may mask important differences among species. Here the variation in sustained swimming ability of the late pelagic stages is examined among species, within two families (Pomacentridae and Chaetodontidae). The pomacentrids displayed a 7.5-fold difference in sustained swimming ability across 24 species, while the chaetodontids displayed a 2-fold difference across 10 species. The variation within the Pomacentridae was not related to pelagic larval duration, post-settlement habitat or taxonomy. There was, however, a significant correlation between sustained swimming ability and total length (TL) of individuals (r=0.435, P〈0.0001). Differences in the mean distance swum by pomacentrid species, however, was most strongly related to differences in mean wet weight (r=0.814, P〈0.0001). When the mean distance swum by species was scaled with respect to mean TL there was still a strong correlation with mean wet weight (r=0.644, P〈0.005). Among chaetodontid individuals TL and sustained swimming ability were not correlated (r=−0.004, P=0.978). Furthermore, sustained swimming ability was not significantly related to the trans-oceanic distribution of species in either family. The variation in sustained swimming ability, however, may contribute to explanations of the observed levels of gene flow within populations.
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    URL: http://dx.doi.org/10.1007/s003380050104
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    Critical comparison of methods for mercury determination in fish (1995)
    Springer
    Microchimica acta 119 (1995), S. 305-310 
    Details
    ISSN: 1436-5073
    Keywords: mercury ; fish ; collaborative study ; atomic absorption spectrometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract One of the major analytical problem in the analysis of fish tissues for total mercury is the dissolution of the sample. This paper compares two different methods of wet digestion (microwave and closed pressurized vessel), followed by FIAAS as final determination and a Zeeman-solid-sample-AAS determination method without previous mineralization. Six fish samples were selected for this study. The top, the central and the bottom portions of the fish were analyzed separately. The mercury contents in the bottom portions determined by Zeeman-solid-sample-AAS were significantly higher than those obtained by the other two systems. A good correlation was observed among the results of the different techniques.
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    URL: http://dx.doi.org/10.1007/BF01244010
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    Comparison of open and closed focussed microwave digestions in view of total mercury determination by cold vapour atomic absorption spectrometry (1995)
    Springer
    Microchimica acta 119 (1995), S. 199-209 
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    ISSN: 1436-5073
    Keywords: microwave digestion ; fish ; mercury ; CVAAS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Food samples digestion, in view to quantify total mercury, is the first step to perform before measuring mercury by cold vapour atomic absorption spectrometry (CVAAS). We have compared two microwave digestion systems, one working at atmospheric pressure (open system) and the other one under pressure (closed system). Results obtained for fish muscle samples by the two methods are in good agreement. However, fat is not digested in the open system, whereas in the closed system no more fat remains in the final solution. During the quantification step, applying the CVAAS technique, we have noticed that the choice and the concentration of the reductant solution is very important to obtain good results. Elaborated methods have been validated using certified reference materials.
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    URL: http://dx.doi.org/10.1007/BF01243999
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    AES investigations of the iron surface composition after laser irradiation under atmospheric conditions (1998)
    Springer
    Microchimica acta 130 (1998), S. 89-95 
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    ISSN: 1436-5073
    Keywords: AES ; laser ; iron ; nitrogen ; oxygen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The laser induced modification of iron surfaces with atmospheric species was investigated by means of Auger electron spectroscopy (AES) and scanning electron microscopy (SEM). Different laser systems were used for irradiating iron samples in a wide range of the laser processing parameters up to small foci and ultra short pulses. A nitriding of iron connected with an oxidation of the near surface region was observed in the wavelength range between 193 nm and 10.6 μm using large foci (∼0.1 cm2) and short pulses (10...1400ns). In case of small foci (∼7·10−6cm2) with ns-pulses (50 ns) an enrichment of the iron melt with nitrogen and an advanced oxidation of the surrounding area of the laser spot were detected. When using shorter pulses (200 fs, 40 ps) no indications for a nitriding were found.
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    URL: http://dx.doi.org/10.1007/BF01254595
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    Forms and nature of organic N in soil (1995)
    Springer
    Nutrient cycling in agroecosystems 42 (1995), S. 1-11 
    Details
    ISSN: 1573-0867
    Keywords: nitrogen ; 15N humic substances ; acid hydrolysis ; analytical pyrolysis ; NMR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Most of the N in surface soils occurs in organic forms. The organic N in soil plays a key role in plant nutrition and soil fertility through its effects on microbial activity and nutrient availability. Typically, about one-third of the fertilizer N applied to temperate-zone soils is immobilized and retained in organic forms at the end of the growing season. A significant portion of this newly immobilized N is no more available to microorganisms and plants than the native humus N. Stabilization processes, probably involving polymerization of amino compounds and polyphenols, result in incorporation of N into humic substances with a concurrent reduction in N availability. This paper presents an account of the forms and nature of organic N in soil, emphasizing possible formation pathways, chemical characterization of humic substances through conventional and solid-state techniques, and the fate and composition of newly immobilized N in soil.
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    URL: http://dx.doi.org/10.1007/BF00750495
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    A conceptual assessment of the importance of denitrification as a source of soil nitrogen loss in tropical agro-ecosystems (1995)
    Springer
    Nutrient cycling in agroecosystems 42 (1995), S. 139-148 
    Details
    ISSN: 1573-0867
    Keywords: denitrification ; methods ; 15N ; nitrate ; nitrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract This paper attempts to answer the question: is denitrification a major route of N loss from tropical agro-ecosystems? This question turns out to be very difficult to answer due to a severe shortage of data on this process for tropical agro-ecosystems other than rice. Given this lack of data, I approach this question by analyzing data on denitrification and nitrous oxide flux in tropical native forest and pasture soils and attempt to make some conclusions and pose some hypotheses about the significance of denitrification in tropical agricultural soils. I also briefly review methods for measuring denitrification. The data analysis suggests that denitrification in tropical forest soils is strongly influenced by the nature and amount of soil C and N turnover. Studies to examine differences in denitrification in different tropical agricultural systems should focus on the effects of system management on C and N turnover. The data analysis also suggests that, just as in temperate regions, denitrification may not be a significant route of N loss from most tropical agricultural systems. However, field studies are necessary to determine if this is actually the case.
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    URL: http://dx.doi.org/10.1007/BF00750508
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    Estimating nutrient surplus and nutrient use efficiency from farm characteristics (1995)
    Springer
    Nutrient cycling in agroecosystems 45 (1995), S. 221-233 
    Details
    ISSN: 1573-0867
    Keywords: fertilizer recovery ; modelling ; nitrogen ; nutrient efficiency ; nutrient surplus ; phosphorus ; Poland
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Research on nutrient losses from agricultural systems should try to relate these losses to farm characteristics. This was done for private farms in two districts in Poland. Using data from a farm survey, nutrient surpluses and Nutrient Use Efficiency (NUE, defined as the ratio of outgoing and incoming nutrients) were calculated for nitrogen and phosphorus. Both nutrient surplus and NUE are relatively high. A model was developed to estimate surpluses and NUE from farm characteristics like location, farm size, fertilizer application level, animal density, grass production and sugar beet or potato area. The results of the model are satisfying for nutrient surplus (R2=0.9) and nitrogen NUE (R2=0.4). Estimation of phosphorus NUE was not satisfactory. High surpluses are associated with high fertilizer applications, high animal density and high grass production while an increasing share of sugar beets leads to lower surpluses. A high nitrogen NUE is associated with low fertilizer applications, low animal density and little grass production, and with a high sugar beet area share. Results suggest that, with exception of sugar beet, fertilizer recovery in Poland is very low. Sugar beet, however, combines high fertilizer applications with low surpluses and high NUE. The outcome of the model can be used in the design of environmental policies. The paper ends with some remarks on the type of measures that can be taken, and the effects these will have on private farms in Poland.
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    URL: http://dx.doi.org/10.1007/BF00748593
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    Influence of co-granulated nutrients and granule size on plant responses to elemental sulfur in compound fertilizers (1996)
    Springer
    Nutrient cycling in agroecosystems 46 (1996), S. 81-90 
    Details
    ISSN: 1573-0867
    Keywords: elemental sulfur ; granule size ; nitrogen ; phosphorus ; potassium ; S oxidation ; sulfur fertilizers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Experiments were undertaken to determine the effect of granule size and nutrients in granulated compound fertilizers fortified with finely divided elemental sulfur (So) on the rate of So oxidation. In one experiment, So was banded together with or apart from triple superphosphate (TSP) while in two others, So was granulated with nutrient and inert carriers. A fourth experiment examined response to S in an So-fortified TSP from a range of granule sizes. Response and, in some cases, So recovery (using 35S labels) by test crops (maize, wheat, upland rice) was measured. In all experiments, P mixed with So increased plant growth and S recovery above treatments in which P and So were physically separated. There was however, no effect of distance of separation on S recovery. In one experiment, N as urea and N and P as diammonium phosphate (DAP) were also found to enhance response to So although to a lesser degree than P alone. These observations were attributed to a nutritional requirement of So-oxidizing microorganisms for P and N. Granulation of So with carriers also influenced oxidation rate, as inferred from the fertilizer S recovery. For a given So concentration, the effect was inversely proportional to the mean diameter of granules. It is shown that this relationship can be explained if one assumes that So particles in granules collapse into a fixed number of aggregates per granule irrespective of granule size when the soluble nutrient carrier dissolves and diffuses away from the point of application.
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    URL: http://dx.doi.org/10.1007/BF00210226
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    Direct emission of nitrous oxide from agricultural soils (1996)
    Springer
    Nutrient cycling in agroecosystems 46 (1996), S. 53-70 
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    ISSN: 1573-0867
    Keywords: crop ; emission ; fertilizer ; nitrogen ; nitrous oxide ; soil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract This analysis is based on published measurements of nitrous oxide (N2O) emission from fertilized and unfertilized fields. Data was selected in order to evaluate the importance of factors that regulate N2O production, including soil conditions, type of crop, nitrogen (N) fertilizer type and soil and crop management. Reported N2O losses from anhydrous ammonia and organic N fertilizers or combinations of organic and synthetic N fertilizers are higher than those for other types of N fertilizer. However, the range of management and environmental conditions represented by the data set is inadequate for use in estimating emission factors for each fertilizer type. The data are appropriate for estimating the order of magnitude of emissions. The longer the period over which measurements are made, the higher the fertilizer-induced emission. Therefore, a simple equation to relate the total annual direct N2O−N emission (E) from fertilized fields to the N fertilizer applied (F), was based on the measurements covering periods of one year: E=1+1.25×F, with E and F in kg N ha-1 yr-1. This relationship is independent of the type of fertilizer. Although the above regression equation includes considerable uncertainty, it may be appropriate for global estimates.
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    URL: http://dx.doi.org/10.1007/BF00210224
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    Effects of temperature on nutrient release from slow-release fertilizers (1996)
    Springer
    Nutrient cycling in agroecosystems 46 (1996), S. 179-187 
    Details
    ISSN: 1573-0867
    Keywords: electrical conductivity ; leaching ; nitrogen ; pH ; phosphorus ; potassium ; release pattern ; slow-release fertilizers ; temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract We studied the effect of temperature on the release of N, P, and K from slow-release fertilizers (SRF). The study was conducted in micro-lysimeters filled with moist peat medium. Increasing the temperature from 4 to 12°C slightly increased N release from three different slow-release N (SRN) carriers with different particle sizes and coating thicknesses. At 21°C the rate of release was significantly different than the other two temperatures. Urea formaldehyde (UF), sulphur coated urea (SCU) and coated calcium nitrate (CCN), incubated in sphagnum moss peat, released between 3 and 20% of the applied N in six weeks. For eight synthetic and organic NPK carriers, the release pattern was similar to UF and SCU. However, the leaching losses of N from the NPK fertilizers were up to twenty times more than for the SRN products. Except for Osmocote® and Duna, which released 30–40% of the applied N as mineral-N within six weeks, all other slow-release and slowly mineralized NPK carriers acted like readily water-soluble compound NPK. Temperature did not affect the nutrient release from NPK fertilizers.
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    URL: http://dx.doi.org/10.1007/BF00420552
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    Evaluation of nitrate leaching risk at site and farm level (1998)
    Springer
    Nutrient cycling in agroecosystems 50 (1998), S. 271-276 
    Details
    ISSN: 1573-0867
    Keywords: nitrogen ; monitoring ; dairy farming ; simulation models ; risk assessment ; soil variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract At the ‘De Marke’ experimental farm a dairy farm was set up with the aim of meeting environmental and economic goals. The farm management with respect to nitrogen emphasized reduction of fertilization and a cattle grazing system that should result in nitrate concentrations in the groundwater below the EC-directive level of 11.3 mg l-1 nitrate-N. At six sites in six different fields of ‘De Marke’, these concentrations were monitored for 4 years. A direct comparison with the chosen limit was possible for these sites, but an evaluation of the environmental achievements of the farming system at farm level was also required. This was achieved by using simulation models and additional information about soils and field management. Based on multiple soil profile descriptions, frequency distributions of model output were generated, allowing a risk assessment for the total farm. The probability of exceeding the chosen threshold value of 11.3 mg l-1 nitrate-N during the period of summer 1991- spring 1995 was 63% for the whole farm, with marked differences between years, crops and hydrological conditions.
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    URL: http://dx.doi.org/10.1023/A:1009704714949
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    Leaching of nitrogen and phosphorus from rural areas to surface waters in the Netherlands (1998)
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    Nutrient cycling in agroecosystems 50 (1998), S. 321-324 
    Details
    ISSN: 1573-0867
    Keywords: nutrient modelling ; leaching ; nitrogen ; phosphorus ; schematization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract In context of preparing the Fourth National Policy Document on Water Management in the Netherlands effects of different scenarios of fertilizer management on nitrogen (N) and phosphorus (P) leaching from rural areas into Dutch surface waters were analyzed. The manuscript offers insight into the model instrument that is used to simulate the different scenarios. Main parts of the modelinstrument are: a procedure to schematize the Netherlands in horizontal areal units, field scale mechanistic models for water and nutrient behaviour in the soil and an empirical model for fertilizer additions.
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    URL: http://dx.doi.org/10.1023/A:1009773202654
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    Can organic farming help to reduce N-losses? (1998)
    Springer
    Nutrient cycling in agroecosystems 52 (1998), S. 277-287 
    Details
    ISSN: 1573-0867
    Keywords: dairy farming ; efficiency ; nitrogen ; organic ; pig farming ; surplus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract This study is in two parts. In the first part, nitrogen (N) losses per unit of milk and meat in Danish conventional and organic pig and dairy farming were compared on the basis of farm data. In the second part, organic and conventional dairy farming were compared in detail, using modelling. N-surpluses at different livestock densities, fodder intensities, and soil types were simulated. Finally, simulated N-surpluses were used in national scenarios for conversion to organic dairy farming in Denmark. In Part one, pig farming was found to have a higher N-efficiency than dairy farming. Organic pig production had a lower N-efficiency and a higher N-surplus per kg meat than conventional pig production. The possibilities to reduce N-loss by conversion to organic pig production therefore appear to be poor. Organic dairy farming had a higher N-efficiency and a lower N-surplus per kg milk than conventional dairy farming. Conversion from conventional to organic dairy farming may therefore reduce N-losses. In Part two, a positive correlation between livestock density and N-surplus ha-1 was found for dairy farming. For all simulated livestock densities, fodder feeding intensities and soil types, organic systems showed a lower N-surplus per unit of milk produced than conventional systems. National scenarios for dairy farming showed that the present Danish milk production could be achieved with a 24% lower total N-surplus if converted from intensive conventional farming to extensive organic farming. At the same time, N-surplus ha-1 and N-surplus (t milk)-1 would be lowered by 50% and 25% respectively. Changing from intensive to extensive conventional dairy farming with a livestock density equal to that in the organic scenario resulted in a reduction in N-surplus ha-1 of 15%. It was concluded that a reduction in total N-loss from agriculture is possible by converting from conventional to organic dairy farming but at the cost of either lower production on the present dairy farm area, or the current production on a substantially larger area.
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    URL: http://dx.doi.org/10.1023/A:1009790722044
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    Food production and consumption in Germany: N flows and N emissions (1998)
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    Nutrient cycling in agroecosystems 52 (1998), S. 289-301 
    Details
    ISSN: 1573-0867
    Keywords: food production and consumption ; mitigation strategies ; nitrogen ; nitrogen emission ; nitrous oxide ; sustainability of human N cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract During the past four decades the authors perceive that an increasing non-sustainability (Disintegration) within the agriculture , human nutrition, waste management complex has occurred both in Germany and the European Union. Compared to the basic needs of the population for nutritive energy, fat and protein, we estimate that the production and consumption of food and feed is more than 50% higher than necessary. Using nitrogen (N) input into German agriculture in 1991/92 as an example, we estimated that the N input of 191 kg ha-1 was 2 to 3 times too high. This high N input resulted in the net biomass production of 45 kg ha-1, a 25% efficiency. This inefficiency causes emissions of reactive N and other nutrient compounds into the hydrosphere and atmosphere that were 2 to 8 times too high. For example the contributions of agriculture to the total annual N2O–N emissions of Germany (during 1990–1992), Europe (1990) and of the world (1989) were 110, 691 Gg and 6.7 Tg or 52, 62 and 41%, respectively. The authors demonstrate that emissions of N and P from Germany and EU waste water management systems are also higher than necessary because nutrient recycling is not practiced extensively. Excessive food production and consumption has made the agriculture/human nutrition/waste and waste water complex, like the energy/transportation complex, a main cause of new transboundary environmental damage such as soil and water acidification, hypertrophication of near-natural terrestrial and aquatic ecosystems and climate change. We propose that a sustainable food production/consumption system can be developed that is based both on need-oriented production and consumption with no net exports and on recovery, recycling and more efficient use of nutrients. Using N as an example, the authors show which short and long term action aims must be set and realized by the year 2015, to meet environmental, economical and social sustainability requisites. The suggested, assumed sustainable N balance for German agriculture is characterized by a critical annual input and surplus maximum of 80 and 45 kg N ha-1 respectively, which should almost double biomass production efficiency for N utilization. This estimate is based on reducing animal stocking rates to 0.5 gross weight unit ha-1 to attain no net mineralization or immobilization of N in the soil.
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    URL: http://dx.doi.org/10.1023/A:1009706001900
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    Retention and leaching of N in Norwegian coniferous forests (1998)
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    Nutrient cycling in agroecosystems 52 (1998), S. 171-178 
    Details
    ISSN: 1573-0867
    Keywords: atmospheric deposition ; boreal forests ; critical loads ; forest growth ; gas losses ; leaching ; nitrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Nitrogen is brought into natural ecosystems from the atmosphere through N-fixation and deposition of NH 4 + and NO 3 - as wet and dry deposition. N is lost from terrestrial ecosystems unaffected by human activities by leaching or as gas, but the losses from different forest-and vegetation types are poorly quantified. The leaching is hampered by uptake in the vegetation and by immobilisation by soil organisms. The gas loss of N in the form of N2O and N2 appears to be rather small, but the loss of NO is unknown. Human activities such as those leading to the increased atmospheric dry and wet deposition of N, may affect the N-losses, but the increase in losses are likely to be very dependent on the amounts of N deposited. The present paper discusses the fate of the N deposited under the existing pollution climate in Norway where N deposition above the natural background has taken place for at least 50 years. The deposition today varies from about 15–20 kg N ha-1 yr-1 in the southernmost parts of the country to background values of about 2 kg ha-1 yr-1 in the north. Even in areas with the highest loads there are no clear indications that N-leaching in forest ecosystems has increased to ‘unacceptable’ levels. The main reason for this appears to be that most of the N deposited are immobilised in forest soils and utilised by forest trees and ground cover vegetation to increased biomass production. At present therefore, no clear signs of N-saturation can be found. This is in relatively good accordance with estimates of critical loads for N in Norwegian coniferous forests. Estimates of immobilisation, gas losses, net uptake in vegetation, biological fixation as well as a figure for ‘acceptable’ leaching, indicate that the long-term critical load of N might be of the order 10 to 30 kg N ha-1 yr-1. Most of the N deposited from the atmosphere appears therefore so far to be retained in the forests and only a small proportion seems to be lost to ground-and surface waters.
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    Effect of split applications of cattle slurry and mineral fertilizer–N on the yield of silage maize in a slurry-based cropping system (1999)
    Springer
    Nutrient cycling in agroecosystems 53 (1999), S. 209-218 
    Details
    ISSN: 1573-0867
    Keywords: cattle slurry ; fertilizer splitting ; nitrogen ; recovery ; residual nitrogen ; Zea mays L
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The recovery of soil mineral nitrogen (N) by crops, and its subsequent utilisation for dry matter (DM) production may be increased when the application of N is postponed until after crop emergence. The significance of this strategy for silage maize was studied in nine field experiments on Dutch sandy soils from 1983 to 1988. In five experiments the effect of slurry applied before planting at a rate of circa 66 m3 ha-1, was compared to the effect of a similar rate of which half was applied before planting and half at the 4–6 leaf stage. In the 4-6 leaf stage slurry was either injected or banded. In four other experiments the effect of mineral fertilizer-N splitting was studied. In these experiments, 30 m3 ha-1 cattle slurry, applied before planting, was supplemented with mineral fertilizer-N at rates ranging from 40 to 160 kg ha-1, either fully applied before crop emergence or split. When split, 40 kg ha-1 of the mineral fertilizer-N rate was banded at the 4–6 leaf stage. According to balance sheet calculations, substantial losses of slurry N and mineral fertilizer-N occurred during the growing season. Losses were compensated for, however, by apparent mineralization, ranging from 0.34 to 0.77 kg N ha-1 day-1. Split applications of cattle slurry had a significant positive effect on the DM yield in two out of five experiments compared to the conventional non-split application, but only when the post-emergence slurry application was banded which is no longer in accordance with present legislation. Split applications of mineral fertilizer-N had a significant positive effect in one experiment where rainfall was excessive but not in the others. The results provide insufficient evidence to recommend farmers to split applications. Soil mineral N sampling at the 4–6 leaf stage should hence be considered a control on the appropriateness of early N applications after exceptional weather conditions rather than a routine observation on which the post-emergence N dressing is to be based in a deliberate splitting strategy. Our data suggest that the financial return of a 40 kg ha-1 supplementation with mineral fertilizer-N, was questionable when more than 175 kg N ha-1 were found in the upper 0.6 m soil layer at the 4–6 leaf stage.
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    Using nitrogen budgets to indicate nitrogen use efficiency and losses from whole farm systems: a comparison of three methodological approaches (1999)
    Springer
    Nutrient cycling in agroecosystems 53 (1999), S. 259-267 
    Details
    ISSN: 1573-0867
    Keywords: farming systems ; nitrogen ; nitrogen budgets ; sustainability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Three approaches to nitrogen budgeting were developed and their ability to quantitatively describe nitrogen cycling in a fertilizer based and a grass–clover based beef system tested. Budgets ranged in complexity from the Economic Input:Output (EIO) budget, which accounted simply for purchases and sales of nitrogen over the farmgate, through the Biological Input:Output (BIO) budget, which included estimates of biological nitrogen fixation and attempted to partition losses into leaching and gaseous forms, to the Transfer:Recycle:Input:Output (TRIO) budget, which also accounted for key soil processes. Nitrogen unaccounted for in the fertilized system decreased with increasing budget complexity (285, 212 and 188 kg ha-1 yr-1 unaccounted for by the EIO, BIO and TRIO budgets, respectively). In the legume based grass–clover system, the EIO budget did not accurately describe total nitrogen inputs as it did not include 146 kg ha-1 yr-1 from symbiotic nitrogen fixation. In the grass–clover system, nitrogen unaccounted for was again greater using the BIO than the TRIO budget (103 and 79 kg ha-1 yr-1, respectively). In conclusion, the most complex budgeting approach (TRIO) was able to account for the fate of a greater proportion of nitrogen inputs than the simpler approaches. However, the perceived success of the different approaches was strongly dependent on the precise objective.
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    Nitrogen uptake and chlorophyll meter measurements in Spring Wheat (1999)
    Springer
    Nutrient cycling in agroecosystems 55 (1999), S. 1-6 
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    ISSN: 1573-0867
    Keywords: chlorophyll meter ; irrigation ; LAI ; nitrogen ; Spring Wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract A Spring Wheat crop was grown using three irrigation levels and nitrogen rate applications to evaluate chlorophyll meter measurements as a possible nitrogen nutrition index for modelling. These measurements yielded the most reliable indications at Zadoks GS45. The lower limit indicating severe nitrogen deficiency in the leaves was approximately 35 SPAD units while the upper limit of 45 SPAD units, indicated an excess consumption.
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    The fate of algal nitrogen in a flooded soil system (1999)
    Springer
    Nutrient cycling in agroecosystems 55 (1999), S. 89-94 
    Details
    ISSN: 1573-0867
    Keywords: algae ; flooded soils ; N cycling ; nitrogen ; 15N ; rice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Algal N labelled with 15N added to a flooded soil in laboratory columns without plants was studied to determine the changes over time in the fate of N assimilated by algae and to study how its fate is affected by (a) exclusion of light simulating complete closure of the rice canopy, and (b) addition of fertilizer-NH4 *. In the light but with no added fertilizer-N there was little net mineralization of the added algal N during the first 4 weeks, but after 8 weeks 42% had been mineralized, of which 95% was denitrified. Exclusion of light caused net mineralization to proceed more rapidly in the first 4 weeks due to the death of algal cells and lowered reassimilation. After 8 weeks 51% had been mineralized, of which 54% was denitrified, 16% volatilized and 30% was present as KCl exchangeable NH4 +-N. Application of fertilizer-NH4 + apparently caused mineralization of 25% of the algal N within one week but the results were probably affected by pool substitution in which labelled N mineralized to NH4 +-N was diluted with fertilizer – NH+ 4 and then immobilized leaving more labelled NH4–N in the mineral pool. After 8 weeks, 42% of algal N had been mineralized, of which 69% was estimated to have been denitrified, 19% lost through NH3 volatilization and 12% remained as extracted NH4 ++NO- 3. Uptake of N by a rice crop would reduce the gaseous losses. Algal N was mineralized quickly enough to be available during the growing season of a rice crop and, depending on field conditions, algae may have a role in assimilating N and protecting it from loss as well as being a major driving force for NH3 volatilization through diurnal increases in pH.
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    15N isotope dilution techniques to study soil nitrogen transformations and plant uptake (1995)
    Springer
    Nutrient cycling in agroecosystems 42 (1995), S. 185-192 
    Details
    ISSN: 1573-0867
    Keywords: 15N ; nitrogen ; soil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The use of15N as a tracer in soil/plant research is examined. The limitations of the so-called Ndff approach are discussed to show the need to consider not just the fate of the added label but also the path that was followed and the rate of the transformation. The development of15N isotope dilution techniques to determine gross rates of nitrogen transformation in soil is reviewed with some indications as to the further development of the approach.
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    The value of poultry manure for wetland rice grown in rotation with wheat (1996)
    Springer
    Nutrient cycling in agroecosystems 47 (1996), S. 243-250 
    Details
    ISSN: 1573-0867
    Keywords: fertilizer value ; nitrogen ; phosphorus ; poultry manure ; urea ; wetland rice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Poultry manure applied alone or in combination with urea at different N levels was evaluated as a N source for wetland rice grown in a Fatehpur loamy sand soil. Residual effects were studied on wheat which followed rice every year during the three cropping cycles. In the first year, poultry manure did not perform better than urea but by the third year, when applied in quantities sufficient to supply 120 and 180 kg N ha−1, it produced significantly more rice grain yield than the same rates of N as urea. Poultry manure sustained the grain yield of rice during the three years while the yield decreased with urea. Apparent N recovery by rice decreased from 45 to 28% during 1987 to 1989 in the case of urea, but it remained almost the same (35, 33 and 37%) for poultry manure. Thus, urea N values of poultry manure calculated from yield or N uptake data following two different approaches averaged 80, 112 and 127% in 1987, 1988 and 1989, respectively. Poultry manure and urea applied in 1:1 ratio on N basis produced yields in between the yields from the two sources applied alone. After three cycles of rice-wheat rotation, the organic matter in the soil increased with the amount of manure applied to a plot. Olsen available P increased in soils amended with poultry manure. A residual effect of poultry manure applied to rice to supply 120 or 180 kg N ha−1 was observed in the wheat which followed rice and it was equivalent to 40 kg N ha−1 plus some P applied directly to wheat.
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    Effect of digested sewage sludge on the efficiency of N-fertilizer applied to barley (1997)
    Springer
    Nutrient cycling in agroecosystems 48 (1997), S. 241-246 
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    ISSN: 1573-0867
    Keywords: barley ; denitrification ; fertilizerefficiency ; mineralization ; nitrogen ; sludge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Enhanced microbial activity following sewage sludge land application may affect soil N cycling and, therefore, plant available N. We studied the effect of anaerobically treated sewage sludge on N-fertilizer efficiency and on some aspects of the soil N cycling. Field plots (3 m × 9 m) sown with barley (Hordeum vulgare L.) in November were amended with a) sludge (80 mg ha-1) and ammonium nitrate (150 kg N ha-1), b) ammonium nitrate (150 kg ha-1) only, c) or left unamended. Monthly soil samples were taken from 0 to 20-and 20 to 50-cm depths to determine soil inorganic N (NH4 +, NO3-). Denitrification in the upper 20-cm horizon was estimated by measuring N2O+N2 emission from undisturbed soil samples by the acetylene-inhibition technique. Crop yield parameters were analysed before harvesting, and grain production was recorded. With respect to the control, the yield increase for the N-fertilizer treatment was 85% and 45% for the sludge + N-fertilizer treatment. The decrease of N-fertilizer efficiency in sludge amended plots was presumably due to a decrease in spring plant available N. Presumably, microbial immobilisation and denitrification in organic amended treatments were responsible for the decrease in N-fertilizer efficiency.
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    Impact of vesicular arbuscular mycorrhizal fungi andRhizobium on the growth and P, N and Fe uptake by faba-bean (1995)
    Springer
    Nutrient cycling in agroecosystems 43 (1995), S. 43-48 
    Details
    ISSN: 1573-0867
    Keywords: Phosphorus ; nitrogen ; iron ; VAM ; Rhizobium ; faba-bean
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The effect of rhizobial inoculation, vesicular arbuscular mycorrhizal (VAM) fungi on the growth, P, N and Fe uptake by faba-bean plants (Vicia faba L.V. Giza 2) grown in virgin sandy soil, treated with super or rock-P were studied under green-house conditions. The earthern pots received a half of the recommended rate of P either as single super phosphate or rock-P in the rate of 20 mg P/kg soil, and calcium ammonium nitrate was added in the rate of 10 mg N/kg soil. Iron was applied in two levels 0 and 5 mg Fe/kg soil, in the form of iron sulphate (FeSO4·7H2O). Dry matter yield, as well as P, N and Fe-uptake were determined. Nodule numbers and their dry weights, spore numbers and mycorrhizal root infection were determined. Results indicated that, fungal infection and rhizobial inoculation either alone or in combination increased dry matter yield as compared to uninoculated plants, whereas the percentages increase in dry matter were 34, 26 and 57% in case of super-P application, while they were 56, 47 and 89% in case of rock-P when inoculated withRhizobium, VAM and dual inoculation respectively. Also P, N and Fe uptake were significantly increased due to inoculation, and dual inoculation resulted the highest effect. Generally, inoculation withRhizobium and/or mycorrhizae can remove the deficient effect of P and Fe on N2-fixation and plant growth in the soil of low nutrients content.
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    URL: http://dx.doi.org/10.1007/BF00747681
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    A global inventory of nitric oxide emissions from soils (1997)
    Springer
    Nutrient cycling in agroecosystems 48 (1997), S. 37-50 
    Details
    ISSN: 1573-0867
    Keywords: greenhouse gases ; nitrogen ; NOx ; nitrous oxide ; ozone precursors ; trace gases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Over 60 published papers reporting field measurements of emissions of nitric oxide (NO) from soil are reviewed, and over 100 annual estimates of NO emissions were made for various types of ecosystems, including agricultural fields. These data were stratified by biome and the mean of each stratum was multiplied by an estimate of the biome area. A few strata were identified as clearly having low NO emissions: montane forests, swamps and marshes, tundra, and temperate forests that are not heavily affected by N deposition. The largest emissions were observed in tropical savanna/woodland, chaparral, and cultivated agriculture, but variation in NO emissions within these strata was also large. Although the stratification scheme fails to partition this within-stratum variation, it does clearly identify these biomes as globally important sources of NO and as areas where more research is needed to investigate within-biome variation in NO emissions. It is too early to tell whether differences in NO emissions between temperate and tropical agriculture are significant, but it is clear that agriculture is an important source of NO and that management practices affect NO emissions. The best current estimate of the global soil source of NO is 21 Tg N yr-1. Adsorption of NOx onto plant canopy surfaces may reduce emissions to the atmosphere to as low as 13 Tg N yr-1, although the absorption effect is probably smaller than this. An error term for the global estimate is difficult to determine, but it is at least ±4 and perhaps as large at ±10 Tg N yr-1. Hence, only modest progress has been made in narrowing uncertainties in the estimate of the global soil source of NO, although some published lower estimates appear unlikely. This inventory reconfirms that the soil source of NO is similar in magnitude to fossil fuel emissions of NOx. Further narrowing of the uncertainty of the estimate of global soil NO emissions will require more sophisticated and carefully chosen stratification schemes to address variation within biomes based on soil fertility, soil texture, climate, and management and will require linking this type of inventory and stratification with mechanistic models.
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    Intercropping sorghum with nitrogen fixing trees in semiarid India (1998)
    Springer
    Agroforestry systems 42 (1998), S. 181-194 
    Details
    ISSN: 1572-9680
    Keywords: Acacia ferruginea ; Albizia lebbeck ; Faidherbia albida ; nitrogen ; sorghum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The influence of three nitrogen fixing tree (NFT) species viz., Faidherbia albida, Acacia ferruginea, Albizia lebbeck and four nitrogen levels (0, 20, 40 and 60 kg N ha−1) on intercropped rainfed sorghum was investigated at Hyderabad, India. The trees were established in shallow alfisols during 1985 with a spacing of 4 × 4 m. Intercropping was done in 1993 and 1994. The effect of trees on radiation interception, soil moisture, crop growth, yield components and yield of sorghum was examined. Association of tree species reduced grain and dryfodder yields of sorghum to an extent of 12 to 40% compared to sole crop situation. The reduction was maximum under A. lebbeck, minimum with F. albida and moderate under A. ferruginea. Application of 40 kg N ha−1 resulted in increased grain and dryfodder yields over other levels. Crop growth in terms of LAI and drymatter had similar response. The receipt of photosynthetically active radiation (PAR) was low under NFTs compared to open situation. The relative PAR intercepted under the trees was in the order: F. albida 〉 A. ferruginea 〉 A. lebbeck. Soil moisture status was more favourable under F. albida than under the other tree species. Soil moisture at all stages of crop growth was more in sole crop situation.
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    Relationships between preference, rumen degradability, gas production and chemical composition of browses (1997)
    Springer
    Agroforestry systems 39 (1997), S. 129-144 
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    ISSN: 1572-9680
    Keywords: fibre ; intake ; nitrogen ; palatability ; tannin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The aim of this work was to assess whether degradability, gas production or chemical constituents could predict the preference of browses. Forty tropical browse species leaves with a crude protein (CP) content ranging from 79 to 307 g kg-1 DM were used for this study. The neutral detergent fibre (NDF) ranged from 220 to 694 g kg-1 DM, while acid detergent fibre (ADF) ranged from 146 to 523 g kg-1 DM. The NDF-bound nitrogen (NDFN) and ADF-bound nitrogen were particularly high in Calliandra calothyrsus, Acacia polyacantha, Sesbania sesban, Acacia venosa and Acacia hockii. High levels of tannins were observed in Acacia species especially A. dolichocephala, A. hockii, A. microbotrya and A. salicina. High levels were also observed in Flemingia macrophyla and Leucaena pallida. The browse species differed (P 〈 0.05) in DM in sacco degradability coefficients. High potential degradability (PD) and effective degradability (ED) were observed in Sesbania spp, Moringa stenopetala, Indigofera arrecta, Chamaecytisus palmensis and Atriplex spp. The browses differed (P 〈 0.05) in asymptotic gas (Ag) production (ml g-1 OM), but had similar (P 〉 0.05) times of incubation at which half of the asymptotic gas had been formed. Preference and DM intake were positively correlated (P 〈 0.01) to NDFN, but negatively correlated (P 〈 0.05) to NDF and ADF. The PD and Ag were negatively (P 〈 0.001) related to NDF, ADF and lignin. Total phenols (TP) and condensed tannins (CT) were negatively (P 〈 0.05) related to PD, ED and Ag. A positive correlation was observed between CT and NDF-bound condensed tannins (r = 0.55, P 〈 0.001) and, CT and TP (r = 0.40, P 〈 0.01). Prediction equations were poor for DM intake and preference, moderate for gas production and good for potential and effective degradabilities. The phenolic components were more related to dry matter degradation and gas production than to preference and dry matter intake. NDFN and Ag made a positive contribution to both preference and DM intake. It was concluded that chemical constitutes such as N, NDF, NDFN, ADF and lignin are essential to predict the nutritive value of browses.
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    Influence of Canopy Height and Fertilization Levels on the Resistance of Lycopersicon Hirsutum to Aculops Lycopersici (Acari: Eriophyidae) (1999)
    Springer
    Experimental and applied acarology 23 (1999), S. 633-642 
    Details
    ISSN: 1572-9702
    Keywords: tomato plants ; susceptibility ; mite ; tridecan-2-one ; nitrogen ; potasium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The objective of this work was to study the effect of NK fertilization levels and canopy height on the resistance of Lycopersicon hirsutum and Lycopersicon esculentum to Aculops lycopersici (Acari: Eriophydae). The effects of NK fertilization levels and canopy height in the leaf size and density of trichomes and their effects on tridecan-2-one (2-TD) and undecan-2-one (2-UD) limiting the attack of A. lycopersici on tomato plants were assessed. Different NK fertilization levels had no effect on the resistance of L. hirsutum to A. lycopersici. No significant differences were found in attack rates of this mite on leaves of the top and median parts of L. hirsutum canopy. The type and density of trichomes were the main determining factor of A. lycopersici attack on tomato plants. High trichome densities and type VI glandular trichomes which produce tridecan-2-one are important resistance factors on tomato plants. L. hirsutum showed a high resistance level to A. lycopersici due to high densities of type VI glandular trichomes and consequently higher levels of tridecan-2-one in its leaves.
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    Landscape-level interactions between topoedaphic features and nitrogen limitation in tallgrass prairie (1995)
    Springer
    Landscape ecology 10 (1995), S. 337-348 
    Details
    ISSN: 1572-9761
    Keywords: fire ; nitrogen ; NDVI ; transect ; watershed
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Transects across watersheds with varying fire histories and remotely-sensed data were used to study vegetation-resource interactions in a tallgrass prairie in Kansas. Paired plots (fertilized, control) were established along these transects and sampled for grass and forb biomass during the 1989 and 1990 growing seasons. Fertilization resulted in significant production responses in grass and total biomass on the west slopes of the annually burned (ID) and infrequently burned (N4) watersheds for both years (p = 0.05). In 1989, fertilization also produced a significant increase in grass biomass on the west slope of the unburned transect (p = 0.05), however, total production was not significantly increased. East slopes were insensitive to nitrogen additions. Differences in production response along these transects were assessed by testing the interaction between fertilization response and slope position. Significant interactions occurred on both 1D and N4, but only in 1990. Production data for both years were also compared to Normalized Difference Vegetation Index (NDVI) values derived from thematic mapper (TM) images for 1989 and 1990. When differences among transects or watersheds were statistically different, a positive relationship between NDVI and biomass was observed. NDVI values accurately reflected the spatial patterns of production along these transects for both years although not necessarily the magnitude.
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    Estimating regional forest productivity and water yield using an ecosystem model linked to a GIS (1998)
    Springer
    Landscape ecology 13 (1998), S. 323-334 
    Details
    ISSN: 1572-9761
    Keywords: forest productivity ; NPP ; runoff ; climate ; nitrogen ; northeastern U.S. ; modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We used the PnET-II model of forest carbon and water balances to estimate regional forest productivity and runoff for the northeastern United States. The model was run at 30 arc sec resolution (approximately 1 km) in conjunction with a Geographic Information System that contained monthly climate data and a satellite-derived land cover map. Predicted net primary production (NPP) ranged from 700 to 1450 g m2 yr1 with a regional mean of 1084 g m2 yr1. Validation at a number of locations within the region showed close agreement between predicted and observed values. Disagreement at two sites was proportional to differences between measured foliar N concentrations and values used in the model. Predicted runoff ranged from 24 to 150 cm yr1with a regional mean of 63 cm yr1. Predictions agreed well with observed values from U.S. Geologic Survey watersheds across the region although there was a slight bias towards overprediction at high elevations and underprediction at lower elevations. Spatial patterns in NPP followed patterns of precipitation and growing degree days, depending on the degree of predicted water versus energy limitation within each forest type. Randomized sensitivity analyses indicated that NPP within hardwood and pine forests was limited by variables controlling water availability (precipitation and soil water holding capacity) to a greater extent than foliar nitrogen, suggesting greater limitations by water than nitrogen for these forest types. In contrast, spruce-fir NPP was not sensitive to water availability and was highly sensitivity to foliar N, indicating greater limitation by available nitrogen. Although more work is needed to fully understand the relative importance of water versus nitrogen limitation in northeastern forests, these results suggests that spatial patterns of NPP for hardwoods and pines can be largely captured using currently available data sets, while substantial uncertainties exist for spruce-fir.
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    Estuarine reconnection of an impounded mangrove salt marsh in the Indian River Lagoon, Florida: short-term changes in fish fauna (1998)
    Springer
    Mangroves and salt marshes 2 (1998), S. 29-36 
    Details
    ISSN: 1572-977X
    Keywords: culverts ; culvert trap ; mosquito impoundment ; seine ; fish
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Fish population dynamics in a 24.3 ha mangrove-dominated mosquito impoundment in east-central Florida were examined by seining and culvert traps before and after installation of culverts that established estuarine connection for the first time in 39 years. In a 27-day period following the culvert opening, fish species increased from 9 to 21, while total number of fish in the impoundment decreased. Movement of fishes through culverts in both directions commenced immediately following culvert opening. Recruitment of transient species into the impoundment appeared to key on a single wind-driven high tide event. Such short-term events may be important cues for fish movement into and out of impounded salt marshes.
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    URL: http://dx.doi.org/10.1023/A:1009969708038
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    Effect of landscape position on the sediment chemistry of abandoned-channel wetlands (1996)
    Springer
    Landscape ecology 11 (1996), S. 27-38 
    Details
    ISSN: 1572-9761
    Keywords: abandoned channels ; floodplain ; nitrogen ; organic matter ; phosphorous ; potassium ; sediment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The nature of sediments in abandoned channels is an important component of their development as floodplain wetlands. The texture, organic matter, phosphorous, potassium, and nitrogen content of sediments were determined for abandoned channels along the Iowa and Cedar Rivers near their confluence in Iowa. Differences in the levels of these constituents were examined among categories of three landscape gradients: present connectivity to the river, time since abandonment, and proximity to agricultural land use. Local scale processes of ecological development are seen in the importance of time for increased organic matter and nitrogen. Basin scale processes of sediment transport and deposition are revealed by the importance of connectivity for decreases in these two elements, and by the counter-intuitive findings for nitrogen and especially phosphorous and potassium in relation to agricultural proximity. Location on a floodplain is important for differentiating development, but it cannot be reduced to univariate gradients.
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    URL: http://dx.doi.org/10.1007/BF02087111
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    A GIS-based index for relating landscape characteristics to potential nitrogen leaching to wetlands (1996)
    Springer
    Landscape ecology 11 (1996), S. 237-255 
    Details
    ISSN: 1572-9761
    Keywords: wetlands ; non-point source pollution ; nitrogen ; watershed ; leaching ; geographic information system ; landscape ; groundwater
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We developed a spatially-explicit, quantitative Nitrogen Leaching Index to assess the potential for non-point source subsurface nitrogen pollution to wetlands. The index was based on the leaching potential of the watershed soils, the amount of nitrogen available for leaching, and the spatial position of nitrogen sources in the watershed. A raster or cell-based geographic information system (GIS) was used to estimate the necessary data inputs for calculating the index, such as soil hydrologic group, land use/soil type combination, groundwater residence time, and location of septic systems. The Total and Average Watershed Nitrogen Leaching Index (TWNLI and AWNLI) were calculated by summing and averaging, respectively, individual cell contributions over a watershed. Analysis of nine wetland watersheds in central New York state, USA, with mixed forest and agricultural land uses illustrated the use of the index for identifying and ranking wetlands with potential nitrogen pollution. Results showed that the spatial characteristics of a watershed potentially can effect subsurface nitrogen delivery to groundwater-dominated wetlands. The use of an index based on watershed soils, topography, and land use may be useful for assessing potential nitrogen pollution to wetlands at a regional scale.
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    URL: http://dx.doi.org/10.1007/BF02071814
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    Prevalence and abundance of two trematode parasites,Diplostomum phoxini andMacrolecithus papilliger in European minnows (Phoxinus phoxinus) in an artificial Swiss Alpine lake (1995)
    Springer
    Aquatic sciences 57 (1995), S. 119-126 
    Details
    ISSN: 1420-9055
    Keywords: Phoxinus phoxinus ; fish ; Diplostomum phoxini ; Macrolecithus papilliger ; parasitism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The influence of parasites on the breeding biology of the European minnow (Phoxinus phoxinus) was studied by examining 268 adult and 59 young-of-the-year minnows from an artificial Swiss Alpine lake for parasites during the breeding seasons in 1990 and 1991. Two trematode parasites;Diplostomum phoxini, in their brains, andMacrolecithus papilliger, in their guts, were found. The prevalence ofD. phoxini was 100% in both years. The mean abundance was 231 in 1990 and 448 in 1991; the difference was significant. Prevalence (and abundance) ofM. papilliger was 37.5% (1.04±0.39) in 1990 and 59.5% (2.68±0.55) in 1991; also significantly higher in 1991 than in 1990. No differences in prevalence or abundance between males and females were found. Numbers of both parasites were significantly correlated with fish length. There was seasonal variation in the abundance ofD. phoxini metacercariae, with a peak in June/July in both years. The prevalence ofM. papiller decreased after July in both years. Distribution of the two trematodes was overdispersed as indicated by the variance to mean (abundance) ratio. The observed seasonal variation inD. phoxini abundance also suggests that sublethal parasites could influence the population dynamics of their hosts.
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    URL: http://dx.doi.org/10.1007/BF00877380
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    Divergent distributions of prey and predator, a fishing effect? (1995)
    Springer
    Aquatic sciences 57 (1995), S. 106-118 
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    ISSN: 1420-9055
    Keywords: Benthos ; fish ; vertical distribution ; predation risk ; selective fishing ; Lake Constance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract To compare the vertical distributions of benthos and fish species of Upper Lake Constance (Bodensee), 552 benthos samples were taken with an Auerbach grab at four transects (10–250 m). An additional 54 samples (1–10 m) were collected elsewhere. Complementary data was taken from the literature. In winter, most fish feed on benthos, mainly chironomids, but in summer less than 5% do so. Formerly the bottom gill-netting aimed mainly at catchingCoregonus pidschian, but it now aims atPerca fluviatilis. Contrary to expectation, in winter the greatest abundance ofP. fluviatilis is much deeper (55 m) than that of its preferred food, i.e. chironomids (〈20 m). Comparably,C. pidschian also stayed deeper than its main food source (chironomids and mollusks).Lota lota, Salvelinus profundus andS. alpinus — unlike the unwanted cyprinids — also stay or stayed deeper than the attractive chironomids. It is argued that the fish reduce their “predation risk”, i.e. the risk of being gillnetted in the upper 50 m, by “selecting” the deeper less dangerous, but also less food-abundant habitat. Balancing predation risk against food abundance may have led to “survival of the deepest”.
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    URL: http://dx.doi.org/10.1007/BF00877379
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    Influence of age, frailty and liver function on the pharmacokinetics of brofaromine (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 387-391 
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    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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    URL: http://dx.doi.org/10.1007/s002280050037
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    Methotrexate in juvenile rheumatoid arthritis (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 507-511 
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    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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    URL: http://dx.doi.org/10.1007/BF00193703
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    Antipyrine disposition in obesity: evidence for negligible effect of obesity on hepatic oxidative metabolism (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 525-530 
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    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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    Oral bioavailability of CHF1194, an inclusion complex of piroxicam and β-cyclodextrin, in healthy subjects under single dose and steady-state conditions (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 531-536 
    Details
    ISSN: 1432-1041
    Keywords: Piroxicam ; β-Cyclodextrin ; pharmacokinetics ; healthy volunteers ; multiple dose ; adverse event
    Source: Springer Online Journal Archives 1860-2000
    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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    Furosemide disposition in patients on CAPD (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 385-390 
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    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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    Effects of altitude (4300 M) on the pharmacokinetics of caffeine and cardio-green in humans (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 167-170 
    Details
    ISSN: 1432-1041
    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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    Pharmacokinetics and bioavailability of a sustained-release diltiazem formulation (Mono-Tildiem LP 300 mg) after repeated administration in healthy volunteers (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 259-264 
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    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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    Disposition of lorazepam in diabetes: differences between patients treated with beef/pork and human insulins (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 253-258 
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    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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    Pharmacokinetics of 5-aminosalicylic acid from controlled-release capsules in man (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 273-277 
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    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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    Pharmacokinetics of thiopental after single and multiple intravenous doses in critical care patients (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 127-137 
    Details
    ISSN: 1432-1041
    Keywords: Thiopental ; Pharmacokinetic modelling ; pharmacokinetics ; single dose ; multiple dosing ; neurosurgical patients ; variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Thiopental was administered to neurosurgical patients for cerebral protection and its pharmacokinetic parameters were determined after a single bolus of 540, 1000 or 1500 mg (3 subjects) or after multiple doses of 250 mg (5 subjects) and 500 mg (2 subjects) every two hours for up to 7 days. The data were analysed by a two- or three- compartment model and linear kinetics. After a single IV bolus, the mean initial volume of distribution (V1) was 0.4811·kg−1, and the steady-state volume of distribution (Vss) was 2.16 1·kg−1. The distribution (t1/2α) and elimination (t1/2β) half-lives were 0.590 and 5.89 h, respectively, and the mean residence time (MRT) was 7.44 h. The clearance was 5.41 ml·min−1·kg−1. With repeated injections, the pharmacokinetic parameters for each patient were estimated taking into account all administered doses and blood samples, which were taken whenever possible daily at steady state and after the last dose. The variability observed in the pharmacokinetic parameters of thiopental reflected by the coefficient of variation (CV%) was wide but was of similar magnitude within patients (CVintra) as it was between patients (CVinter). The steady-state trough plasma concentration (Cmin obs) ranged from 4.8 to 30 mg·1−1 (mean 16.0 mg·1−1 and median 14.3 mg·1−1). Peak concentrations (Cmax obs) ranged from 8.35 to 45 mg·1−1 (25.4 mg·1−1, and median 23.3 mg·1−1). The values of V1 and Vss were similar to those obtained after a single dose. For V1, the mean was 0.333 1·kg−1. The mean Vss was 2.68 1·kg−1, with a CVintra of 12.6 to 56% and a CVinter of 13.2%. A shorter distribution half-life t1/2α was noted on multiple dosing; the mean value was 0.122 h. The elimination half-life t1/2β and the mean residence time became longer due to a decrease in clearance. For t1/2β the mean value was 16.3 h. The mean MRT was 21.9 h, CVintra 9.19 to 48.5%, and the CVinter 35.3%. The mean clearance was 2.16 ml·min−1·kg−1, CVintra 7.28 to 25.5%, and the CVinter 20.4%. This value is 50% lower than after a single dose. Identification of the kinetic parameters of thiopental allows simulation of the effects of doses on subsequent plasma levels and will permit a priori prediction of day to day adjustment of drug dosage.
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    Limitations of the maximum entropy principle in devising drug input rate (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 139-143 
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    ISSN: 1432-1041
    Keywords: Intestinal absorption ; Amoxicillin ; pharmacokinetics ; maximum entropy ; input rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A computer program applying the principle of maximum entropy to the analysis of drug absorption rate has been developed. Plasma concentrations of amoxicillin obtained after oral and intravenous dosing have been analysed, together with simulated data corresponding to a complex input. Amoxicillin absorption rates devised by the program were similar to those obtained by a standard deconvolution method, although they were displayed as an almost continuous profile. However, improbable fluctuations were obtained with some data sets and the fraction absorbed was underestimated by 13%. With the simulated data, the maximum entropy program did not provide a better solution than the standard deconvolution procedure, and it was sensitive to the addition of random error and to the number of samples. The maximum entropy principle, as implemented in our computer program, may not have a better performance than standard deconvolution procedures, especially in human experiments where the number of blood samples is usually limited.
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    Design of a suitable formulation of FK613, a novel antiallergic agent, based on its pharmacokinetic and pharmacodynamic properties in healthy subjects (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 279-284 
    Details
    ISSN: 1432-1041
    Keywords: Antiallergic drug ; FK613 ; pharmacokinetics ; histamine skin-test ; drug formulation ; urinary excretion ; safety
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetic and pharmacodynamic properties of FK613, a novel indolyl piperidine derivative, were investigated after oral administrations of 5, 10 and 20 mg in hard gelatin capsules to healthy male volunteers. FK613 was rapidly and almost completely absorbed, and 〉89% was recovered in the urine as the unchanged form. The urinary excretion of FK613 was linearly correlated with plasma concentration and its low water solubility was the main concern regarding the safety. In another experiment using a double-blind crossover design, in which 0 (placebo), 5 and 20 mg FK613 were administered to determine the plasma concentration-effect relationship, suppression of the intradermal histamine-induced skin reaction by FK613 was observed. Thus, the maintenance of a plasma concentration of FK613 in the range of 80–250 ng · ml-1 was recommended to ensure the suppression of histamine-induced wheal by 〉50% and not to exceed the solubility in urine. To achieve this, a new hydrogel-type formulation of FK613 was developed, with the aim both of delaying its absorption, so as to suppress the sharp rise in plasma concentration, and of maintaining the effective concentration for a longer period of time. This formulation was administered after meals at the doses of 20, 30, 40, 50 and 60 mg, and at repeated doses of 40 mg twice daily for 6.5 days to evaluate the pharmacokinetics and safety in healthy subjects. The area under the plasma concentration curve increased linearly with dose, whereas maximum plasma concentration (Cmax) tended to peak as dose increased, indicating the desirable properties of this formulation. Although Cmax exceeded 250 ng/ml at doses of 30 mg or more, no urinary crystal formation was observed on careful inspection of urine.
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    Influence of an acidic beverage (Coca-Cola) on the absorption of itraconazole (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 235-237 
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    ISSN: 1432-1041
    Keywords: Key words Itraconazole ; Coca Cola; acidic beverage ; absorption ; pharmacokinetics ; drug concentration ; food
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To evaluate the effectiveness of Coca-Cola in enhancing the absorption of itraconazole. Methods: Eight healthy volunteers were randomized to receive two treatment sequences in a two-way crossover design with a 1-week wash-out period separating each study treatment. Treatment I, the control, consisted of 100 mg itraconazole with 325 ml water. Treatment II was identical to treatment I, except that itraconazole was administered with 325 ml of Coca-Cola (pH 2.5). Results: Serum itraconazole concentrations, after administration with Coca-Cola (treatment II), were higher than after administration with water (treatment I). The mean AUC was 1.12 vs 2.02 μg · h · ml−1, the mean Cmax was 0.14 vs 0.31 μg · ml −1and the mean tmax was 2.56 vs 3.38 h in treatments I and II, respectively. Conclusion: The absorption of itraconazole can be enhanced by Coca-Cola.
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    Pharmacokinetics of nicardipine enantiomers in healthy young volunteers (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 289-292 
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    ISSN: 1432-1041
    Keywords: Key words Nicardipine; enantiomers ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: The present study was conducted to compare pharmacokinetic behaviors of nicardipine enantiomers given in different doses with different formulations of racemic nicardipine in healthy volunteers. Methods: One or two 20-mg racemic nicardipine tablets, and a 40-mg sustained-release capsule of nicardipine were administered to eight healthy volunteers in a cross-over fashion and pharmacokinetic parameters were evaluated. Enantiomer concentrations were determined by GC-MS combined with chiral stationary phase HPLC. Results and conclusions: Serum concentration of (+)-nicardipine was approximately 2–3 times higher than that of (−)-nicardipine in 20- and 40-mg doses of conventional formulations and a non-linear increase in bioavailability with dose was demonstrated. The value for AUC of (+)-nicardipine was approximately 2.3–2.8 times greater than that of the (−)-nicardipine (P 〈 0.05) when 20 and 40 mg racemic nicardipine were administered in a conventional preparation. Relative bioavailability of the sustained-release preparation vs the conventional preparation was 28% and 44% for (+)- and (−)-nicardipine, respectively, for the 40-mg dose.
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    URL: http://dx.doi.org/10.1007/s002280050292
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    Transdermal nitroglycerin: clinical and pharmacokinetic consequences of renewing the patch and the application site (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 379-381 
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    ISSN: 1432-1041
    Keywords: Key words Nitroglycerin; transdermal nitrate ; pharmacokinetics ; patch renewal ; exercise test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: We examined whether nitroglycerin (glyceryl trinitrate, GTN) patch treatment for 24 h could induce local cutaneous changes that impaired drug delivery and clinical efficacy. Methods: Twenty angina patients were exercise-tested after 2 and 24 h of treatment and then 2 h after patch renewal. The patch was either renewed on a new skin location or on the previous application site in a randomised, double-blind, cross-over protocol. GTN plasma concentrations and finger plethysmography were obtained before and after each exercise test. Results and conclusions: The clinical efficacy, the effect seen on plethysmography and the GTN plasma concentrations tended to increase after patch renewal, regardless of the application site of the renewed patch. Hence, cutaneous changes of clinical importance could not be demonstrated.
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    URL: http://dx.doi.org/10.1007/s002280050304
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    Pharmacokinetics and pharmacodynamic effects of the angiotensin II antagonist valsartan at steady state in healthy, normotensive subjects (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 441-449 
    Details
    ISSN: 1432-1041
    Keywords: Key words Angiotensin II ; Valsartan; AT1 receptor antagonist ; healthy volunteers ; pharmacokinetics ; renin-angiotensin system ; blood pressure ; passive tilting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Pharmacokinetics, pharmacodynamic effects and tolerability of 200 mg valsartan, once-daily for 8 days, were investigated in 16 healthy, normotensive volunteers on a normal sodium diet. Methods: This was a double-blind, placebo-controlled, randomized crossover study. Drug concentrations in plasma and urine, angiotensin II (Ang II) concentrations in plasma, systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) in the supine position and 3 min after passive head-up tilting, as well as safety parameters (ECG, clinical chemistry and hematology, renal water and electrolyte excretion) were measured over 24 h after the first dose (day 1) and at steady state on day 8. Results: Absorption and distribution of valsartan were rapid (Cmax, 2 h; t½λ1 〈 1 h), followed by a slower terminal elimination phase (t½λ2, 6 h) on days 1 and 8, with little accumulation in plasma (increase of 20% on day 8). Less than 10% of the dose was excreted unchanged in urine. The increase in plasma Ang II (Cmax, 6 h) was significantly enhanced at steady state. Supine SBP and DBP significantly decreased on day 8 only, by an average of −3.6 and −2.4 mmHg, respectively, versus placebo, without a concomitant increase in HR. Upon passive tilting, the increase in DBP, normally reinforced by sympathetic renin release, was slightly but significantly blunted on day 1 (−2.0 mmHg) and day 8 (−4.0 mmHg) of treatment with valsartan versus placebo. The orthostatic reflex increase in HR was slightly enhanced compared with placebo by an average of 2.8 beats · min−1 on day 1 and by 2.9 beats · min−1 on day 8. Valsartan was well tolerated and had no influence on ECG, clinical laboratory parameters, and water, electrolyte and uric acid excretion. Conclusions: Pharmacokinetics of valsartan are unchanged after multiple once-daily dosing, with little (expected) accumulation in plasma. Effects of 200 mg valsartan on blood pressure in healthy subjects on a normal sodium intake are small and become more prominent after repeated dosing. Indirect evidence of AT1 blockade by valsartan is demonstrated by an increase of plasma Ang II and by a blunted DBP response to passive tilting. The decrease in blood pressure at steady state enhances the increase in plasma Ang II. Valsartan is well tolerated and is devoid of effects on water, electrolyte and uric acid excretion at 200 mg per day in healthy normotensive volunteers.
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    URL: http://dx.doi.org/10.1007/s002280050317
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    Multiple dose pharmacokinetics of tiludronate in healthy volunteers (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 175-181 
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    ISSN: 1432-1041
    Keywords: Key words Tiludronate; healthy volunteers ; bisphosphonates ; pharmacokinetics ; calcium metabolism ; bone resorption ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: A double-blind, placebo-controlled study was conducted to assess the pharmacokinetics and pharmacodynamics of the bisphosphonate tiludronic acid, administered once daily as sodium tiludronate 200, 400, 600 and 800 mg for 12 days. Four groups of ten subjects participated in the study, with a drug to placebo ratio of 4:1. Methods: Pre-dose blood samples were taken on alternate days, starting on Day 1 and additional samples were collected over 144 h following the final dose on Day 12. Urine was collected over 24 h after the final dose. Indices of calcium homeostasis and biochemical markers of bone turnover were assessed during the study as pharmacodynamic parameters. Tolerability was evaluated with special emphasis on renal function and gastrointestinal irritation. Adverse experiences were assessed at regular time intervals. Results and conclusions: Steady state was attained from Day 4 (200 mg) or from Day 6 (400, 600 and 800 mg). Following the final dose on Day 12, minimal plasma concentrations (Cmin) ranged between 0.19 and 1.5 mg ⋅ l−1, and maximal plasma concentrations (Cmax) between 1.1 and 7.8 mg⋅l−1 for the lowest and highest doses, respectively. A supra-proportional increase in Cmax, AUC24 and Ae 24 with dose was observed. There was a linear relationship between the plasma tiludronic acid and its urinary excretion rate, so, the disproportional rise in Cmax and AUC24 with increasing dose could not be attributed to saturation of renal excretion. Certain indices of calcium homeostasis changed significantly during the study, but generally, became only prominent at the highest dose level of 800 mg. Total serum calcium and the urinary calcium/creatinine clearance ratio fell, indicating depression of osteoclastic bone resorption, which was not revealed by serum osteocalcin levels probably because of the brevity of the treatment (12 days). In response to the decline in serum calcium, serum 1,25-dihydroxyvitamin D3 and intact PTH (1–84) levels increased. None of the safety parameters raised any concerns about the safety of sodium tiludronate administered in this way.
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    Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 189-193 
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    ISSN: 1432-1041
    Keywords: Key words Dihydropyridine ; Amlodipine ; Grapefruit juice; flavonoids ; interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: This study was performed to assess whether coadminstration with grapefruit juice significantly affects the pharmacokinetics of amlodipine, a dihydropyridine class calcium antagonist with slow absorption, distribution and low plasma clearance. The primary objective was to evaluate whether short exposure to grapefruit juice could affect the metabolism of amlodipine to an extent similar to that previously demonstrated for other dihydropyridines (e.g. felodipine, nisoldipine, nitrendipine). Methods: Twelve healthy male volunteers followed a randomised, open crossover study design, comparing the effect of a single oral dose of amlodipine (5 mg) taken together with a glass of grapefruit juice (250 ml) vs water. Blood samples to determine plasma concentration were taken and blood pressure (BP) and heart rate (HR) were measured throughout the study. Results: When amlodipine was coadministered with grapefruit juice, Cmax was 115% and AUC(0–72 h) was 116% compared with water, but tmax was not significantly changed. There were no significant differences in BP and HR between the two treatments. A small decrease in diastolic BP, however, was observed in both treatments 4–8 h after drug administration, coinciding with Cmax, but this was normalised after 12 h. The BP reduction seen was compensated by a slight increase in HR, which remained throughout the study. Conclusion: An interaction between grapefruit juice and amlodipine was demonstrated. The haemodynamic data showed that a dose of 5 mg was sufficient to achieve a BP reduction in healthy subjects, but the increase in amlodipine plasma concentration seen after intake of grapefruit juice was too small to significantly affect BP or HR. The clinical significance of this food/drug interaction, however, cannot be ignored since there is considerable variation between individuals and a more extensive intake of grapefruit juice might give more pronounced effects.
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    URL: http://dx.doi.org/10.1007/s002280050183
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    Haemodynamic effects and pharmacokinetics of oral d-and l-nebivolol in hypertensive patients (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 259-264 
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    ISSN: 1432-1041
    Keywords: Key words Nebivolol ; Hypertension; d ; l-enantiomers ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Nebivolol is a selective β1-adrenergic receptor blocker possessing an ancillary vasodilating effect. The objective of the present study was to study the haemodynamic and pharmacokinetic properties of nebivolol 5 mg once daily in a double-blind, placebo-controlled cross-over study. Methods: Fifteen patients, 12 men and 3 women, with essential hypertension were investigated. Blood pressure and peripheral circulation were determined after acute oral nebivolol administration, 5 mg daily, and after 4 weeks treatment. Results: The acute effect on blood pressure upon single-dosing was weak and non-significant. After 4 weeks both systolic blood pressure (152 vs 163 mmHg) and diastolic blood pressure (89 vs 97 mmHg) were significantly reduced after nebivolol treatment as compared to placebo. Following the first dose the venous volume was higher on placebo (5.88 ml ⋅ 100 ml−1 tissue) as compared to active nebivolol treatment (5.17 ml ⋅ 100 ml−1 tissue), while there were no statistically significant differences with regard to venous plethysmographic findings after 1 month on placebo (5.53 ml ⋅ 100 ml−1 tissue) or on active treatment (5.97 ml ⋅ 100 ml−1 tissue). Calculated peripheral resistance did not differ between active treatment (617 units) or placebo (548 units) after the first dose, whereas it was significantly lowered after 4 weeks of nebivolol treatment (483 units) as compared to placebo (593 units). Conclusions: Oral nebivolol 5 mg once daily lowered blood pressure and heart rate during steady state compared to placebo. Moreover, venous volume was reduced during acute but not steady-state dosing, while peripheral resistance was unaffected in the acute phase but reduced during steady state. Plasma concentrations of the separate enantiomers plus hydroxylated metabolites after the first and last dose in hypertensive patients were similar to those in healthy subjects.
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    URL: http://dx.doi.org/10.1007/s002280050194
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    Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 277-281 
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    ISSN: 1432-1041
    Keywords: Key words Pantoprazole; Proton pump inhibitor drug interaction ; oral anticoagulant phenprocoumon ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Pantoprazole is a selective proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzymes in man. Due to the clinical importance of an interaction with anticoagulants, this study was carried out to investigate the possible influence of pantoprazole on the pharmacodynamics and pharmacokinetics of phenprocoumon. Methods: Sixteen healthy male subjects were given individually adjusted doses of phenprocoumon to reduce prothrombin time ratio (Quick method) to about 30–40% of normal within the first 5–9 days and to maintain this level. The individual maintenance doses remained unaltered from day 9 on and were administered until day 15. Additionally, on study days 11–15, pantoprazole 40 mg was given per once daily. As a pharmacodynamic parameter, the prothrombin time ratio was determined on days 9 and 10 (reference value) and on days 14 and 15 (test value), and the ratio test/reference was evaluated according to equivalence criteria. Results: The equivalence ratio (test/reference) for prothrombin time ratio was 1.02 (90% confidence interval 0.95–1.09), thus fulfilling predetermined bioequivalence criteria (0.70–1.43). The pharmacokinetic characteristics AUC0–24h and Cmax of S(−)-and R(+)-phenprocoumon were also investigated using equivalence criteria. Equivalence ratios and confidence limits of AUC0–24h and of Cmax of S(−)-phenprocoumon (0.93, 0.87–1.00 for AUC0–24h; 0.95, 0.88–1.03 for Cmax) and of R(+)-phenprocoumon (0.89, 0.82–0.96; 0.9, 0.83–0.98) were within the accepted range of 0.8–1.25. Conclusion: Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level. Concomitant treatment was well tolerated.
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    URL: http://dx.doi.org/10.1007/s002280050198
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    Cardiovascular effects of different infusion rates of sufentanil in patients undergoing coronary surgery (1997)
    Springer
    European journal of clinical pharmacology 51 (1997), S. 359-366 
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    ISSN: 1432-1041
    Keywords: Key words Sufentanil ; pharmacokinetics ; haemo dynamics ; different infusion rates ; coronary surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract    Objective: Pharmacokinetics and haemodynamic effects of a total dose of 15 μg · kg−1 sufentanil, an opioid anaesthetic agent, were studied in patients undergoing aortocoronary bypass surgery at three infusion rates of 30 (group I), 5 (group II), and 2 (group III) μg · kg−1 · min−1, respectively. Results: Plasma concentrations of sufentanil could be optimally characterized by a linear biexponential pharmacokinetic model. Non-compartmental analyses indicated that there was no significant difference in the values of clearance (11.6, 13.3, 14.3 ml · min−1 · kg−1), steady-state volume of distribution (0.220, 0.255 and 0.331 l · kg−1) and mean residence time (18.8, 13.3 and 14.3 min) among the groups. The observed mean Cmax values of 421 (group I), 125 (group II), and 53 (group III) ng · ml−1 and observed mean AUC values from 0 to 3 min were all consistent with the dosing regimens. There were large inter-individual variations in haemodynamic response. Compared to plasma data, a delay in haemodynamic effects was found. Times to reach peak haemodynamic effect ranged from 4.3 to 4.9 min for group I, from 4.6 to 6.1 min for group II, and from 9.9 to 11.3 for group III. Except heart rate, peak haemodynamic effects in these study patients generally ranged from 20.9% to 35.2%. Significant reductions in the area under the effect-time profiles of mean arterial blood pressure and systemic vascular resistance were observed in group II and group III, but not in group I. Significant reductions in the area under the effect-time profiles of left ventricular stroke work index were observed in group III only. No effect on heart rate was found in any group. Conclusion: Our findings suggested that a slower infusion rate of sufentanil at a dose of 15 μg · kg−1 tends to give a greater reduction in mean arterial blood pressure, systemic vascular resistance, and left ventricular stroke work index than does a faster infusion rate.
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    Effect of route of administration of fluconazole on the interaction between fluconazole and midazolam (1997)
    Springer
    European journal of clinical pharmacology 51 (1997), S. 415-419 
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    ISSN: 1432-1041
    Keywords: Key words Midazolam ; Fluconazole ; CYP3A4 ; interaction ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Midazolam is a short-acting benzodiazepine hypnotic extensively metabolized by CYP3A4 enzyme. Orally ingested azole antimycotics, including fluconazole, interfere with the metabolism of oral midazolam during its absorption and elimination phases. We compared the effect of oral and intravenous fluconazole on the pharmacokinetics and pharmacodynamics of orally ingested midazolam. Methods: A double-dummy, randomized, cross-over study in three phases was performed in 9 healthy volunteers. The subjects were given orally fluconazole 400 mg and intravenously saline within 60 min; orally placebo and intravenously fluconazole 400 mg; and orally placebo and intravenously saline. An oral dose of 7.5 mg midazolam was ingested 60 min after oral intake of fluconazole/placebo, i.e. at the end of the corresponding infusion. Plasma concentrations of midazolam, α-hydroxymidazolam and fluconazole were determined and pharmacodynamic effects were measured up to 17 h. Results: Both oral and intravenous fluconazole significantly increased the area under the midazolam plasma concentration-time curve (AUC0–3, AUC0–17) 2- to 3-fold, the elimination half-life of midazolam 2.5-fold and its peak concentration (Cmax) 2- to 2.5-fold compared with placebo. The AUC0–3 and the Cmax of midazolam were significantly higher after oral than after intravenous administration of fluconazole. Both oral and intravenous fluconazole increased the pharmacodynamic effects of midazolam but no differences were detected between the fluconazole phases. Conclusion: We conclude that the metabolism of orally␣administered midazolam was more strongly inhibited by oral than by intravenous administration of fluconazole.
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    Lack of interaction between meloxicam and warfarin in healthy volunteers (1997)
    Springer
    European journal of clinical pharmacology 51 (1997), S. 421-425 
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    ISSN: 1432-1041
    Keywords: Key words Warfarin ; Meloxicam ; interaction ; pharmacokinetics ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The effect of multiple oral doses of meloxicam 15 mg on the pharmacodynamics and pharmacokinetics of warfarin was investigated in healthy male volunteers. Warfarin was administered in an individualized dose to achieve a stable reduction in prothrombin times calculated as International Normalized Ratio (INR) values. Then INR- and a drug concentration-time profile was determined. For the interaction phase, meloxicam was added for 7 days and then INR measurements and the warfarin drug profiles were repeated for comparison. Overall, warfarin treatment lasted for 30 days. Results: Warfarin and meloxicam were well tolerated by healthy volunteers in this study. Thirteen healthy volunteers with stable INR values entered the interaction phase. Prothrombin times, expressed as mean INR values, were not significantly altered by concomitant meloxicam treatment, being 1.20 for warfarin alone and 1.27 for warfarin with meloxicam cotreatment. R- and S-warfarin pharmacokinetics were similar for both treatments. Geometric mean (% gCV) AUCSS values for the more potent S-enantiomer were 5.07 mg · h · l−1 (27.5%) for warfarin alone and 5.64 mg · h · l−1 (28.1%) during the interaction phase. Respective AUCSS values for R-warfarin were 7.31 mg · h · l−1 (43.8%) and 7.58 mg · h · l−1 (39.1%). Conclusion: The concomitant administration of the new non-steroidal anti-inflammatory drug (NSAID) meloxicam affected neither the pharmacodynamics nor the pharmacokinetics of a titrated warfarin dose. A combination of both drugs should nevertheless be avoided and, if necessary, INR monitoring is considered mandatory.
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    Genetic polymorphism of CYP2C19 and lansoprazole pharmacokinetics in Japanese subjects (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 391-396 
    Details
    ISSN: 1432-1041
    Keywords: Key words Lansoprazole ; CYP2C19; genotype ; hydroxy lation ; polymorphism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: We investigated whether interindividual differences in the pharmacokinetic disposition of lansoprazole are attributed to the genetic polymorphism of CYP2C19 which occurred by two mutations, CYP2C19m1 and CYP2C19m2, in 20 Japanese subjects. Methods: Polymerase chain reaction (PCR) restriction fragment length polymorphism procedures were used to detect the CYP2C19m1 mutation in exon 5 and the CYP2C19m2 mutation in exon 4 using SmaI and BamHI, respectively. Results: Ten subjects were homozygous (wt/wt subjects) for the wt allele in both exon 5 and exon 4, four subjects were heterozygous (wt/m1) for the CYP2C19m1 mutation, and two subjects were heterozygous (wt/m2) for the CYP2C19m2. The remaining four subjects had both mutated alleles in CYP2C19 genes, i.e., two were homozygous (m1/m1) for the defect in exon 5 and two were heterozygous (m1/m2) for the two defects in exons 5 and 4. The subjects in group 1 (wt/wt, wt/m1 and wt/m2) were the extensive metabolizers (EMs) for 5-hydroxylation of lansoprazole and were in the range of hydroxylation indexes from 3.83 to 19.8, whereas the subjects in group 2 (m1/m1 and m1/m2) were the poor metabolizers (PMs) and the indexes were in the range of 38.5 to 47.6. In group 2, AUC, t1/2 and CL/f of lansoprazole were significantly greater, longer, and lower, respectively, than those in group 1. Conclusion: The hydroxylation of lansoprazole to 5-hydroxylansoprazole was apparently impaired in the subjects with the genetic defects of CYP2C19 (m1/m1 or m1/m2).
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    Influence of age, frailty and liver function on the pharmacokinetics of brofaromine (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 387-391 
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    ISSN: 1432-1041
    Keywords: 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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    Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 411-415 
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    ISSN: 1432-1041
    Keywords: Moxisylyte ; pharmacokinetics ; intracavernous administration ; healthy volunteers ; adverse events ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The concentration-time profiles of specific metabolites of moxisylyte, an α-adrenoceptor blocking agent, in the plasma and urine from 18 healthy volunteers were investigated after intracavernous (IC) administrations at three dose levels (10, 20 and 30 mg). Results: Four metabolites, unconjugated desacetyl-moxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulphates were found in plasma and urine. For all metabolites, t1/2 elimination was independent of the administered dose (1.19 h for unconjugated DAM; 1.51 h for DAM glucuronide; 1.51 h for DAM sulphate; and 2.17 h for MDAM sulphate). Cmax and AUC increased in direct proportion to dose, except for the inactive DAM glucuronide. Any the differences detected were small and equivalence of the three doses can be accepted. Conclusion: The pharmacokinetics of moxisylyte in humans following intracavernous administration were linear in the dose range 10 to 30 mg.
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    Single dose pharmacokinetics of sumatriptan in healthy volunteers (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 543-548 
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    ISSN: 1432-1041
    Keywords: Sumatriptan ; pharmacokinetics ; single dose ; bioavailability ; dose proportionality ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Sumatriptan is classified as a vascular 5HT1 receptor agonist and is effective in the acute treatment of migraine and cluster headache. Sumatriptan is available as an injection for subcutaneous administration and as a tablet for oral administration. The pharmacokinetics of sumatriptan differ depending on the route of administration. The mean subcutaneous bioavilability is 96% compared to 14% for the oral tablet. The lower bioavailability following oral administration is due mainly to presystemic metabolism. The inter-subject variability in plasma sumatriptan concentrations is greater following oral administration and a faster rate of absorption of drug into the systemic circulation is achieved following subcutaneous dosing. The pharmacokinetics of sumatriptan are linear up to a subcutaneous dose of 16 mg. Following oral dosing up to 400 mg, the pharmacokinetics are also linear, with the exception of rate of absorption, as indicated by a dose dependent increase in time to peak concentration. Sumatriptan is a highly cleared compound that is eliminated from the body primarily by metabolism to the pharmacologically inactive indoleacetic acid analogue. Both sumatriptan and its metabolite are excreted in the urine. Although the renal clearance of sumatriptan is only 20% of the total clearance, it exceeds the glomerular filtration rate, indicating that sumatriptan undergoes active renal tubular secretion. Sumatriptan has a large apparent volume of distribution (170 1) and an elimination half-life of 2 h. Oral doses of sumatriptan were administered as a solution of dispersible tablets and subcutaneous dosing was by injection into the arm. In clinical practice, sumatriptan is administered as a film coated tablet or by subcutaneous injection into the thigh.
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    The pharmacokinetics of granisetron, a 5-HT3 antagonist in healthy young and elderly volunteers (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 519-520 
    Details
    ISSN: 1432-1041
    Keywords: Granisetron ; pharmacokinetics ; elderly ; tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194344
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  • 83
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    Pharmacokinetics and pharmacodynamics of a single dose of recombinant human growth hormone after subcutaneous administration by jet-injection: comparison with conventional needle-injection (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 69-72 
    Details
    ISSN: 1432-1041
    Keywords: Growth hormone ; Jet-injection ; pharmacokinetics ; pharmacodynamics ; Somatomedin C ; free fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and pharmacodynamics of recombinant human growth hormone (rhGH) were studied after a single subcutaneous dose given by jet-injection, and have been compared with the results obtained after conventional needle-injection. Twelve healthy male volunteers completed an open label, randomised, two-way crossover study, with a 7-day washout period between the two single sc doses. Pharmacokinetic parameters were derived from rhGH concentrations in blood samples collected regularly over 24 h after dosing on Day 1 of each period. To investigate the pharmacodynamics, additional samples were taken for the analysis of somatomedin C (IGF-I) and free fatty acids (FFA). A higher and earlier Cmax was found after jet-injection (ratio (%) jet-injected/needle-injected 124; 90%-confidence interval 108 – 142). The AUC0−∞ for rhGH were similar (ratio (%) jet-injected/needle-injected 98; 90%-confidence interval 93 – 103). Both treatments were associated with a significant and similar rise in IGF-I. Both administrations of rhGH were associated with identical rhythmical changes in FFA. The study indicates that jet-injected and needle-injected rhGH are bioequivalent with respect to the amount absorbed. The criterion for bioequivalence is not met for the rate of absorption. It is unlikely that the latter finding will influence the pharmacodynamics of rhGH, since bioequipotency was established for the effect on IGF-I generation. Jet-injection was safe in use and was generally well tolerated.
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  • 84
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    Effects of cimetidine on pharmacokinetics and pharmacodynamics of losartan, an AT1-selective non-peptide angiotensin II receptor antagonist (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 115-119 
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    ISSN: 1432-1041
    Keywords: Losartan ; Cimetidine ; pharmacokinetics ; plasma renin activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract This was a 2-period randomized, crossover study in 8 healthy males to determine the effects of cimetidine (400 mg q.i.d. for 6 days) on the pharmacokinetics and pharmacodynamic effects of the angiotensin II receptor antagonist, losartan (100 mg). Cimetidine increased the AUC for losartan 18% without affecting the AUC for E-3174, the active metabolite of losartan. The increase in plasma renin activity following losartan was not affected by cimetidine (maximum mean increases 12.6 and 12.1 ng Ang I·ml−1·h−1 without and with cimetidine, respectively). These results indicate that cimetidine does not appear to alter the pharmacokinetics or pharmacodynamics of losartan to a clinically significant extent.
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    URL: http://dx.doi.org/10.1007/BF00192369
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  • 85
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    Lack of relationship between quinidine pharmacokinetics and the sparteine oxidation polymorphism (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 501-504 
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    ISSN: 1432-1041
    Keywords: Quinidine ; CYP2D6 ; Sparteine oxidation polymorphism ; (3S)-3OH-quinidine ; quinidine-N-oxide ; dihydroquinidine ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Quinidine is a very potent inhibitor of CYP2D6, but the role of the enzyme in the biotransformation of quinidine has only been investigated in a single in vitro study and in two small in vivo experiments, with contradictory results. The present investigation was designed to present definite evaluation of whether quinidine is metabolised by CYP2D6. Eight poor metabolizers (PM) and 8 extensive metabolizers (EM) of sparteine each took one oral dose of 200 mg quinidine. In the EM, the total clearance, the clearance via 3-hydroxylation and the clearance via N-oxidation, were 33, 3.7 and 0.23 l·h−1, respectively. In the PM, the corresponding values were 29, 3.1 and 0.18 l·h−1, respectively. There were no statistically significant differences between EM and PM in any of these pharmacokinetic parameters. It is concluded that CYP2D6 is not an important enzyme for the oxidation of quinidine.
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    URL: http://dx.doi.org/10.1007/BF00194341
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  • 86
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    Single-dose pharmacokinetics of nefazodone in healthy young and elderly subjects and in subjects with renal or hepatic impairment (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 221-228 
    Details
    ISSN: 1432-1041
    Keywords: Nefazodone ; Geriatric assessment ; Hepatic cirrhosis ; Renal impairment ; pharmacokinetics ; antidepressive agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The single-dose pharmacokinetics of nefazodone (NEF) and its metabolites hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP) were examined in 12 healthy younger subjects ≤55 years of age (YNG), 12 elderly subjects ≥65 years of age (ELD), 12 patients with biopsy proven hepatic cirrhosis (HEP) and 12 patients with moderate renal impairment (REN), ClCR 20–60 ml·min−1. The study was of parallel group design, with each of the four subject groups receiving escalating single oral doses of 50, 100 and 200 mg of nefazodone at 1 week intervals. Serial blood samples for pharmacokinetic analysis were collected for 48 h following each dose and plasma samples were assayed for NEF, HO-NEF and mCPP by a validated HPLC method. Single oral doses up to 200 mg of nefazodone were well tolerated by all subjects. Maximum plasma levels of NEF and HO-NEF were generally attained within 1 h after administration of nefazodone. HO-NEF and mCPP plasma levels were about 1/3 and 〈1/10 those of NEF, respectively. There were no apparent gender-related pharmacokinetic differences in any group of subjects. NEF and HO-NEF pharmacokinetics were dose dependent in all four subject groups; a superproportional increase in AUC and an increase in t1/2 with increasing dose was obtained, indicative of nonlinear pharmacokinetics. Relative to normal subjects, elderly and cirrhotic subjects exhibited increased systemic exposure to NEF and HO-NEF, as reflected by AUC, at all doses of nefazodone; subjects with moderate renal impairment did not. Elderly and cirrhotic patients may require lower doses of NEF to achieve and maintain therapeutic effectiveness.
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    URL: http://dx.doi.org/10.1007/BF00192383
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  • 87
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    Steady-state pharmacokinetics of nefazodone in subjects with normal and impaired renal function (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 229-235 
    Details
    ISSN: 1432-1041
    Keywords: Nefazodone ; Renal impairment ; pharmacokinetics ; antidepressive agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The steady-state pharmacokinetics of nefazodone (NEF) and its metabolites hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP) were compared in subjects with normal and impaired renal function. Patients: The Study was of parallel group design which included 7 subjects with normal (NOR) renal function, CLCR≥72 ml·min−1·1.73 m−2, 6 with moderate (MOD) renal impairment, CLCR 31–60 ml·min−1·1.73 m−2 and 9 with severe (SEV) renal impairment, CLCR≤30 ml·min−1·1.73 m−2. Subjects in each renal function group received a 100-mg oral dose of nefazodone hydrochloride BID for 7 days and a single morning dose on day 8. Starting 48 h after the last 100-mg dose, 200-mg doses were administered on a similar schedule to 3, 4 and 3 subjects from each renal function group (NOR, MOD and SEV, respectively). Single trough blood samples just prior to each morning dose (Cmin) and serial samples after the dose on day 8 were obtained at each dose level for pharmacokinetic analysis. Plasma samples were assayed by a specific HPLC method for NEF, HO-NEF and mCPP. The CMIN data indicated that steady state was attained by the third day of BID administration of both the 100- and 200-mg doses of nefazodone, regardless of degree of renal function. Both NEF and HO-NEF attained steady-state Cmax within 2 h after administration of nefazodone; tmax for mCPP was less defined and more delayed. HO-NEF and mCPP plasma levels were about 1/3 and 〈1/10 those of NEF, respectively, regardless of the status of renal function. Steady-state systemic exposure of NEF and HO-NEF, as reflected by AUC and Cmax, and elimination t1/2 values did not differ significantly among renal function groups. Conclusion: The study results suggest that dose adjustments may not be necessary, but nefazodone should be used with caution in the presence of severe renal impairment.
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  • 88
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    Rectal pharmacokinetics of budesonide (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 293-298 
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    ISSN: 1432-1041
    Keywords: Key words Budesonide; enema ; pharmacokinetics ; healthy subjects ; hepatic bypass
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2–43%) and 15% (3.2–50%) after rectal administration and 6.3% (2.4–10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol ⋅ l−1 (0.95–8.2), 3.0 nmol ⋅ l−1 (0.64–8.9) and 1.3 nmol ⋅ l−1 (0.61–3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax = 1.3 h for both formulations (range 0.5–2.0)], but was slower after oral dosing [tmax = 2.1 h (1.0–6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55–99%). The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects.
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  • 89
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    Relationship of changes in felodipine pharmacokinetics to haemodynamics during chronic oral treatment of congestive heart failure patients (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 203-210 
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    ISSN: 1432-1041
    Keywords: Felodipine ; pharmacokinetics ; haemodynamics ; congestive heart failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract In congestive heart failure patients the kinetics of felodipine, a dihydropyridine calcium antagonist, show interpatient differences after acute i.v. administration that disappear after 8 weeks oral treatment with a change in kinetics in the patients with the largest clearances (CL) and the smallest volumes of distribution (V SS). Pharmacokinetic and haemodynamic data were combined to construct a haemodynamic-pharmacokinetic model. This model shows that the differences between the patients in i.v. pharmacokinetics are consistent with a difference in plasma flow distribution between liver and poorly perfused tissues. In patients in whom kinetics changed, felodipine treatment is supposed to cause a redistribution of flow from liver to peripheral tissues, accompanied by a decreased work load of the heart and a larger increase in VO2max during therapy than in the other patients, whose workload increased. This suggests a better therapeutic response in the patients whose kinetics changed. As change in kinetics is related to felodipine CL and CL to liver plasma flow, felodipine CL or even indocyanine CL might be predictive for the therapeutic effect of felodipine.
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  • 90
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    The tolerability, pharmacokinetics and lack of effect on plasma cholesterol of 447C88, an AcylCoA:Cholesterol Acyl Transferase (ACAT) inhibitor with low bioavailability, in healthy volunteers (1995)
    Springer
    European journal of clinical pharmacology 49 (1995), S. 243-249 
    Details
    ISSN: 1432-1041
    Keywords: Cholesterol acyltransferase ; Hypocholesterolaemic ; 447C88 ; volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract 447C88 (N-Heptyl-N′-(2,4 difluoro-4-6-(2(-4-(2,2 dimethylpropyl)phenyl)ethyl)phenyl)urea) is an inhibitor of human microsomal AcylCoA:Cholesterol acyltransferase (ACAT) with an IC50 of 10.2 ng·ml−1 (23 nM). It is poorly absorbed but 5 mg·kg−1·day−1 completely abolishes the rise in plasma cholesterol in cholesterol-fed rats. In this study, twelve healthy, male volunteers received single, oral doses of 25, 50, 100, 200, 400 and 800 mg of 447C88 (n+8) or placebo (n+4) with food in a double-blind study with at least a week between occasions. The 400 mg dose was repeated after an overnight fast. Subsequently, fourteen different volunteers received a single 200 mg dose of 447C88 (n+8) or placebo (n+6) with food and, a week later, the same dose twice daily for 10 days; all doses were given with food. All doses were well tolerated with no significant changes in vital signs, full blood counts or plasma biochemical profiles. Plasma concentrations of 447C88 were unquantifiable after the fasting dose and low after all other doses. Mean Cmax and AUC were 1.8 ng·ml−1 and 9.0 ng·ml−1·h after 200 mg rising to 5.4 ng·ml−1 and 23.8 ng·ml−1·h respectively after 800 mg; t1/2 was 1.3 to 5.2 h. After 10 days dosing, plasma 447C88 concentrations were higher in the evening than the morning probably due to administration of the evening dose with more food. There were no significant changes in plasma triglcerides or total, LDL- or HDL-cholesterol after dosing with 447C88.
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  • 91
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    Rectal pharmacokinetics of budesonide (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 293-298 
    Details
    ISSN: 1432-1041
    Keywords: Budesonide ; enema ; pharmacokinetics ; healthy subjects ; hepatic bypass
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2–43%) and 15% (3.2–50%) after rectal administration and 6.3% (2.4–10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol·l-1 (0.95–8.2), 3.0 nmol·l-1 (0.64–8.9) and 1.3 nmol·l-1 (0.61–3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax=1.3 h for both formulations (range 0.5–2.0)], but was slower after oral dosing [tmax=2.1 h (1.0–6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55–99%). The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects.
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  • 92
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    Increase in magnesium plasma level after orally administered trimagnesium dicitrate (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 317-323 
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    ISSN: 1432-1041
    Keywords: Magnesium ; Plasma level ; pharmacokinetics ; bioavailability ; circadian fluctuation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Magnesium plasma concentrations were measured in healthy probands before and after administration of trimagnesium dicitrate by the oral and intravenous routes. There was a notable circadian fluctuation of the plasma concentration with a peak in the evening hours. After oral administration of 12 and 24 mmol magnesium, a long-lasting, statistically significant increase in plasma magnesium concentration measured as the increase in area under the curve (AUC) between 0 and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%, respectively. The decline in the plasma magnesium concentration after i.v. administration was compatible with a three-compartment model with a terminal half-time of about 8 h. Although no absolute value of the oral bioavailability of trimagnesium dicitrate could be determined from the data, our results may be important in helping to elucidate the influence of magnesium preparations on the plasma magnesium concentration. By comparing the effects of different preparations, it should be possible to estimate the relative oral bioavailability and the bioequivalence of these preparations.
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  • 93
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    Multiple-dose clinical pharmacology of the catechol-O-methyl-transferase inhibitor tolcapone in elderly subjects (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 47-55 
    Details
    ISSN: 1432-1041
    Keywords: Key words Tolcapone ; Elderly; levodopa ; pharmacokinetics ; pharmacodynamics ; multiple-dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: The purpose of this study was to assess the multiple-dose clinical pharmacology of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor, in elderly subjects. Methods: The drug was administered orally t.i.d. for 7 days to four sequential groups of eight elderly subjects (gender ratio1:1) at doses of 100, 200, 400 and 800 mg in a double-blind, randomised, placebo-controlled, ascending-multiple-dose design. On days 2 and 7, a single dose of levodopa/benserazide 100/25 mg was given 1 h after the first intake of tolcapone. Plasma concentrations of tolcapone, its metabolite 3-O-methyltolcapone, levodopa and 3-O-methyldopa were determined during the course of the study in conjunction with COMT activity in erythrocytes. Results: Tolcapone was well tolerated at all dose levels, with a slight increase in gastrointestinal adverse events in females at higher doses. The drug was rapidly absorbed and eliminated and showed no changes in pharmacokinetics with time during multiple doses of 100 and 200 mg t.i.d. At doses of 400 and 800 mg t.i.d., tolcapone accumulated moderately as reflected in increased Cmax and AUC values. Despite the long half-life of 3-O-methyltolcapone (39 h), only minor accumulation occurred due to suppression of its formation by tolcapone. The pharmacodynamics of tolcapone did not change during the week of treatment as reflected in inhibition of COMT activity in erythrocytes, the derived parameters of the plasma concentration-effect relationship (inhibitory Emax model with constant EC50 values) and the effect on levodopa pharmacokinetics (1.6 to 2.5-fold increase in bioavailability). This suggests the absence of tolerance development and the insignificance of the altered pharmacokinetics at 400 and 800 mg t.i.d. with regard to the pharmacodynamics. Conclusion: The results of this study offer promising perspectives for the application of tolcapone as adjunct therapy to levodopa in the treatment of Parkinson’s disease.
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    A comparison of the pharmacokinetics and pharmacodynamics of cilazapril between Chinese and Caucasian healthy, normotensive volunteers (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 57-62 
    Details
    ISSN: 1432-1041
    Keywords: Key words Cilazapril ; Caucasians ; Chinese; cilazaprilat ; pharmacokinetics ; pharmacodynamics ; ACE inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Methods: The pharmacokinetics and pharmacodynamics of the angiotensin converting enzyme (ACE) inhibitor cilazapril were studied in 12 Chinese and 13 Caucasian, healthy, normotensive volunteers on their normal diet. Cilazapril was given orally as a single 2.5 mg capsule. Plasma was sampled for assay of the active metabolite, cilazaprilat, plasma renin activity (PRA), aldosterone, angiotensin I (AI) and ACE-activity. Plasma concentrations of the active drug were measured by radioimmunoassay. Blood pressure and heart rate were measured at regular intervals. Results: The pharmacokinetic parameters of cilazaprilat were similar in the two ethnic groups. No significant difference in plasma concentrations was found at any of the time points. However, the weight-adjusted plasma clearance was significantly higher in the Chinese group, which is compatible with their lower body weight. The effects on plasma hormones were also comparable, although there was a somewhat greater rise in PRA and greater fall in aldosterone levels in Chinese than in Caucasians. The effect of cilazapril on blood pressure and heart rate was greater than was previously reported in healthy volunteers. Systolic (SBP) and diastolic (DBP) blood pressure were significantly reduced in both groups, but there was a more prolonged reduction in DBP in Caucasians. In addition, heart rate (HR) was significantly increased from baseline from 5 h onwards in Chinese subjects and significantly higher in comparison with Caucasians at most time points from 1.5 h onwards. The pharmacokinetic parameters of cilazapril were essentially the same in healthy, normotensive Chinese and Caucasians. Cilazapril reduced blood pressure acutely in both groups, with good tolerance. The inhibition of ACE in relationship to time and the plasma concentrations of cilazaprilat were similar in the two groups, although the changes in PRA and aldosterone suggest an ethnic difference in the responses of the renin-angiotensin-aldosterone system.
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  • 95
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    Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium antagonist felodipine (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 203-208 
    Details
    ISSN: 1432-1041
    Keywords: Key words Cyclosporine ; Felodipine; dehydrofelodi-pine ; pharmacokinetics ; blood pressure ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: In a double blind, randomised, placebo-controlled, cross-over study 12 healthy male volunteers were allocated to receive felodipine + placebo, cyclosporine + placebo, and felodipine + cyclosporine in order to investigate the interaction between the calcium channel blocker felodipine and cyclosporine as it affects the pharmacokinetics of felodipine, dehydrofelodipine, and cyclosporine, and 24-hour blood pressure measurements. Methods: Single doses of cyclosporine (capsules, 5 mg/kg body weight) and of felodipine (extended release (ER) tablets 10 mg) were given at a 1–2 week interval. Plasma drug concentrations were followed for 2 days after drug intake. Results: For cyclosporine, Cmax was increased after combined treatment (16%) compared to cyclosporine alone, but felodipine did not influence other kinetic parameters of cyclosporine. For felodipine, combined treatment with cyclosporine and felodipine increased AUC and Cmax (58% and 151%, respectively) and lowered mean residence time (24%) significantly compared to felodipine alone. For the metabolite dehydrofelodipine, too, AUC and Cmax were increased after the combined treatment (43% and 94%, respectively). Mean 24-hour systolic and diastolic blood pressures were significantly lower after felodipine, both when felodipine was given alone (121/68 mmHg) and in combination with cyclosporine (122/68 mmHg) compared to cyclosporine alone (127/73 mmHg). Conclusion: A combined single dose of cyclosporine and felodipine in healthy subjects increased the AUC and Cmax of felodipine suggesting a cyclosporine-induced decrease in the first-pass metabolism of felodipine, whereas the AUC of cyclosporine was only slightly increased by felodipine.
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    Effect of food on the bioavailability of oxybutynin from a controlled release tablet (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 221-223 
    Details
    ISSN: 1432-1041
    Keywords: Key words Oxybutynin; effect of food ; N-desethyl oxybutynin ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The effect of food on the bioavailability of oxybutynin was assessed in a randomised cross-over study in 23 healthy volunteers. A single oral 10 mg dose of a controlled release oxybutynin tablet was administered after a high fat breakfast and to fasting subjects. The AUC, Cmax, tmax, t1/2 and MRT of oxybutynin and its active metabolite N-desethyloxybutynin were determined. Results: Breakfast did not change the AUC of oxybutynin but increased the AUC of N-desethyloxybutynin by about 20% . The Cmax of oxybutynin and N-desethyl oxybutynin were two-fold higher when the drug was administered after breakfast compared to the fasting state. Conclusion: Breakfast significantly reduced the MRT of oxybutynin and N-desethyloxybutynin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050096
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  • 97
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    Effects of grapefruit juice ingestion – pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 139-145 
    Details
    ISSN: 1432-1041
    Keywords: Key words Felodipine ; Dietary interaction ; Flavonoids; pharmacodynamics ; pharmacokinetics ; grapefruit juice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To examine the effect of grapefruit juice on the metabolism of felodipine following intravenous and oral administration. Methods: The study had a randomised, four-way, crossover design in 12 healthy males. Single doses of felodipine were given as an intravenous infusion for 1 h (1.5 mg) or as an oral extended release (ER) tablet (10 mg). Grapefruit juice (150 ml) or water was ingested 15 min prior to drug intake. Results: Intake of grapefruit juice did not significantly alter the intravenous pharmacokinetics of felodipine compared to control treatment, whereas after oral drug administration it did lead to an increase in the mean AUC and Cmax by 72% and 173%, respectively, and the mean absolute bioavailability was increased by 112%. The fraction of the oral felodipine dose reaching the portal system was increased from 45% to 80% when intake of drug was preceded by grapefruit juice ingestion. The pharmacokinetics of the primary metabolite, dehydrofelodipine, was affected by the intake of juice, resulting in a 46% increase in Cmax. Juice intake immediately before oral felodipine resulted in more pronounced haemodynamic effects of the drug as measured by diastolic blood pressure and heart rate. However, the haemodynamic effects of the intravenous administration were not altered by juice intake. Vascular-related adverse events were reported more frequently when oral drug administration was preceded by juice intake compared with control treatment. Taking grapefruit juice immediately prior to intravenous felodipine administration did not cause any alteration in the adverse event pattern. Conclusion: The main acute effect of the grapefruit juice on the plasma concentrations of felodipine is mediated by inhibition of gut wall metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050263
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  • 98
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    Electronic Resource
    Pharmacokinetics and bioavailability of oral and intramuscular artemether (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 307-310 
    Details
    ISSN: 1432-1041
    Keywords: Key words Artemether ; Thai males; malaria ; dihydroartemisinin ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics and bioavailability of artemether and dihydroartemisinin were investigated in eight Thai males following the administration of single oral and intramuscular doses of artemether (300 mg) in a randomized two-way cross-over study. Results: Both oral and intramuscular artemether were well-tolerated. In most cases, artemether and dihydroartemisinin were detected in plasma after 30 min and declined to levels below the limit of detection within 18–24 h. Compared with intramuscular administration, oral administration of artemether resulted in a relatively rapid but incomplete absorption [Cmax: 474 vs 540 ng · ml−1; t max: 2.0 vs 3.9 h; AUC: 2.17 vs 5.20 μg · h · ml−1]. Geographic means of lag-time and absorption half-life (t 1/2a) of oral vs intramuscular artemether were 0.28 and 1.1 h vs 0.30 and 2 h, respectively. t 1/2z was significantly shortened after the oral dose [2.8 vs 6.9 h]. Mean oral bioavailability relative to intramuscular administration was 43.2%. The ratio of the AUCs of artemether to dihydroartemisinin was significantly lower after the oral than after the intramuscular dose (geometric mean: 0.29 vs 0.60).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050295
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  • 99
    Electronic Resource
    Electronic Resource
    Itraconazole moderately increases serum concentrations of oxybutynin but does not affect those of the active metabolite (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 403-406 
    Details
    ISSN: 1432-1041
    Keywords: Key words Oxybutynin ; Itraconazole; N-desethyloxy‐butynin; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Oxybutynin has low oral bioavailability due to an extensive presystemic metabolism. It has been suggested that the biotransformation of oxybutynin is dependent on CYP3A. Because itraconazole, a widely used mycotic, is a potent inhibitor of CYP3A4, we wanted to study a possible interaction between oxybutynin and itraconazole. Methods: In this double-blind, randomized, two-phase cross-over study, ten healthy volunteers received either 200 mg itraconazole or placebo for 4 days. On day 4, each volunteer ingested a single dose of 5 mg oxybutynin. Serum concentrations of oxybutynin, its active metabolite N-desethyloxybutynin, and itraconazole were monitored over 24 h. Results: Itraconazole significantly increased both the area under the serum drug concentration-time curve (AUC0–t) and the peak concentration of oxybutynin twofold. The AUC0–t and the peak concentration of N-desethyloxybutynin were not significantly affected by itraconazole. Itraconazole did not change the peak time or the elimination half-life of either oxybutynin or N-desethyloxybutynin. The occurrence of adverse events after oxybutynin administration was not increased by itraconazole. Conclusions: Itraconazole moderately increases serum concentrations of oxybutynin, probably by inhibiting the CYP3A-mediated metabolism. However, the concentrations of N-desethyloxybutynin were practically unchanged. Since about 90% of the antimuscarinic activity of oxybutynin is attributable to N-desethyloxybutynin, any interaction of oxybutynin with CYP3A4 inhibiting drugs has only minor clinical significance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050309
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  • 100
    Electronic Resource
    Electronic Resource
    Plasma concentrations and pharmacokinetics of idebenone and its metabolites following single and repeated doses in young patients with mitochondrial encephalomyopathy (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 167-169 
    Details
    ISSN: 1432-1041
    Keywords: Key words Idebenone; mitochondrial encephalomyopathy ; young patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics and tolerance of idebenone after single or repeated doses have been studied in young patients with mitochondrial encephalomyopathy. Results: No significant adverse effects were noted. In 3 out of 7 patients idebenone induced overall stimulation and improvement in arousal. Plasma concentrations of idebenone and its main metabolites were determined and the pharmacokinetic parameters of idebenone after single and repeated doses were estimated. During the single dose study, the mean plasma concentrations of idebenone and its main metabolites and mean pharmacokinetic parameters were comparable to published results (Cmax = 452.2 ng ⋅ ml−1, tmax = 2.3 h, AUC = 26 μg ⋅ ml−1 ⋅ h, t1/2β = 16.5 h). During the repeated doses study, no significant difference was found between mean residual plasma concentrations of idebenone on Day 2 (47 ng ⋅ ml−1) and Day 5 (70.6 ng ⋅ ml−1), and mean t1/2β of idebenone after the single and after repeated dose studies, i.e., there was no evidence of accumulation. Although idebenone did not appear to accumulate during this study, the coadministration of anticonvulsants, often prescribed during mitochondrial encephalomyopathy, can affect its pharmacokinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050179
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