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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 213-219 
    ISSN: 1432-1041
    Keywords: thiamine ; plasma level ; pharmacokinetics ; nonlinear renal elimination ; assay for clinical use
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A sensitive assay for thiamine suitable for clinical use has been developed. It is based on precolumn oxidation of thiamine to thiochrome followed by HPLC-separation and fluorescence detection. The assay is applicable to various biological materials, including human plasma. The minimum amount detectable was 5 fmol, minimum plasma concentration 0.5 nmol/l and minimum sample volume 0.3 ml plasma. Each chromatographic run took 3 min. Inter- and intra-assay relative standard deviations (RSD) were 8.3% and 6.3%, respectively, at a stock plasma concentration of 10.8 nmol/l. At 38.8 nmol/l, interassay RSD was reduced to 3.4%. The recovery of 5 nmol/l added thiamine was 102 (SD±17)%, that of 30 nmol/l was 94±5%. Plasma levels in 91 volunteers ranged from 6.6 to 43 nmol/l, showing a log normal distribution with a median of 11.6 nmol/l. Thiamine kinetics were studied in plasma and urine from 8 men after intravenous and oral doses of 50, 100 and 200 mg thiamine hydrochloride. In all individuals, nonlinear renal elimination kinetics were demonstrated by plotting the fractional amount of thiamine excreted unchanged in urine against the corresponding area under the plasma concentration — time curve.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 38 (1990), S. 237-242 
    ISSN: 1432-1041
    Keywords: cyclosporin A ; diltiazem ; pharmacokinetics ; kidney transplantation ; drug metabolism ; cytochrome P-450 ; drug interactions ; human liver microsomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous reports have indicated that administration of the calcium antagonist diltiazem results in major changes in the pharmacokinetics of cyclosporin A (CyA). A new clinical trial was undertaken in 22 renal transplant patients receiving a constant dose of cyclosporin to further explore this interaction. Coadministration of diltiazem for one week produced an increase in the blood concentration of CyA and its metabolites 17 and 18 in almost all patients, but no increase in CyA metabolites 1 and 21. The mean whole blood CyA trough level determined by HPLC rose from 117 ng·ml−1 to 170 ng·ml−1 after one week on diltiazem, and the mean trough level of metabolite 17 rose similarly from 184 ng·ml−1 before to 336 ng·ml−1. Based on experiments with microsomes from human liver the effect of diltiazem was due to noncompetitve inhibition of CyA-metabolism by diltiazem, and the increased concentration of metabolite 17 might have been due to stronger inhibition of its secondary metabolism steps.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 43 (1992), S. 209-210 
    ISSN: 1432-1041
    Keywords: Moxonidine ; Hydrochlorothiazide ; pharmacokinetics ; drug interaction ; steady-state ; healthy volunteers ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 45 (1993), S. 585-587 
    ISSN: 1432-1041
    Keywords: Flumazenil ; benzodiazepine ; absorption ; disposition ; elderly volunteers ; pharmacokinetics ; aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open design, randomised, two-way cross-over study, a single 2 mg i.v. dose and a single 30 mg oral dose of flumazenil were each administered to a group of healthy young (n=6) and elderly (n=12) volunteers (male: female 2/1). Plasma samples were collected at intervals and intact drug was assayed. Both the IV and oral doses of flumazenil were very well tolerated by both age groups and no severe or unexpected adverse effects were observed. The main complaints were dizziness and headache, mainly after oral dosing, probably due to the higher Cmax and AUC following this route of administration. After 2 mg i. v. the disposition parameters in the two age groups (elderly/young) were very similar: volume of distribution (Vss): 0.88/0.901·kg−1; total body clearance (ClPL): 0.86/0.99 l·min−1; terminal elimination half-life (t1/2β): 1.02/0.91 h. After the 30 mg oral dose the mean Cmax of 87.6 ng·ml−1 (elderly) and 78.4 ng·ml−1 (young) were generally reached within 0.5 to 1 h. In 26% (elderly) and 23% (young), the absolute bioavailability of flumazenil was very similar. It is concluded that the absorption and disposition paramters of flumazenil were not significantly affected by aging.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Euphytica 31 (1982), S. 493-502 
    ISSN: 1573-5060
    Keywords: Quantitative genetics ; selection index ; size of cross progenies ; pedigree method
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary The response to selection is determined by the genetic and nongenetic variance, the selection intensity, and the size of the experiments. If, in pure line breeding, selection starts in segregating generations, the gain depends on the relation of additive to epistatic variance. The gain can be increased if an index is constructed using the information from relatives. From animal breeding this kind of selection is known as combined selection. In this paper the optimal number of families and subfamilies is determined that will maximise the selection response by combined selection for a fixed total size of experiments. The composition of the genetic variance has a imited influence on the optimal size of the progenies. If epistatic variance is important, then the number of F2 families has to be reduced and the number of F3 families and F4 families must be increased. The same is true if the nongenetic variance is increased.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Euphytica 33 (1984), S. 447-454 
    ISSN: 1573-5060
    Keywords: Self-fertilizing crops ; quantitative genetics ; selection index ; size of cross progenies ; combined selection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary In autogamous species the optimum number of families is calculated for a selection program in two stages conducted in segregating generations. The influence of epistasis is not large. In case of much epistasis the number of families at the first stage must be reduced. In comparison with selection in later generations the second stage is relatively important. Two stage selection is more efficient than combined selection.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Euphytica 28 (1979), S. 453-456 
    ISSN: 1573-5060
    Keywords: Self fertilizing crops ; vegetatively propagated crops ; number of crosses ; size of cross progenies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary This short paper discusses the optimum number of crosses and size of progenies for a given total population size to minimize the risk of not finding any favourable genotype in the breeding material. It is shown that the number of crosses must generally be as large as possible. In special situations it may be advantageous to include also less promising crosses instead of enlarging the progenies of more promising crosses.
    Type of Medium: Electronic Resource
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