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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 54 (1998), S. 287-294 
    ISSN: 1432-1041
    Keywords: Key words Drug development ; Nephrotoxicity ; Pro- teinuria ; Albuminuria ; α1-Microglobulin ; N-Acetyl-β-d-glucosaminidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The quantitative measurement of urinary marker proteins may improve the sensitivity of monitoring renal function in healthy male subjects in phase I studies. Little is known about the variability of physiological proteinuria in young, healthy male subjects. Thus, the biological and analytical variability of three marker proteins, i.e. albumin, α1-microglobulin and N-acetyl-β-d-glucosaminidase (NAG), were investigated in this population. Methods: Seven young, healthy male subjects participated in a prospective two-way cross-over study, and 139 in a retrospective study. Albumin and α1-microglobulin were determined by immunological methods (radial immunodiffusion and/or kinetic nephelometry), and NAG by enzyme activity in a colorimetric assay. Results: The inter-assay precision of NAG, albumin and α1-microglobulin is good (〈15%) if automated kinetic nephelometry is applied for albumin and α1-microglobulin determination, but less impressive (〈25%) with radial immunodiffusion. The highest frequency of detectable proteinuria and highest creatinine-adjusted protein levels are found in the second morning urine voided after a night's rest. The intra-individual biological variability of NAG excretion from day to day is low (CV: 15–25%), irrespective of outpatient or inpatient settings. By contrast, albumin and α1-microglobulin excretion can differ by a factor of 2–3 from day to day, and higher levels are predominantly found in outpatient settings. The reference ranges for young, healthy male subjects are generally lower than published in cross-sectional studies in the total healthy population. Conclusion: These findings and established reference ranges for young, healthy male subjects may assist in the evaluation of proteinuria in clinical pharmacological phase I trials.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Nimodipine ; Cimetidine ; Ranitidine ; pharmacokinetic interaction ; cytochrome P-450 ; healthy volunteers ; haemodynamics ; drug interation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A possible interaction between the calcium antagonist nimodipine and the H2-receptor antagonists cimetidine and ranitidine has been investigated in two separate studies in healthy subjects. In eight young volunteers the concomitant administration of nimodipine 30 mg t.i.d. and cimetidine 1000 mg/d for 7 days led to a significant increase of the relative bioavailability of nimodipine. The changes in the pharmacokinetic parameters were not accompanied by discernible haemodynamic effects or any change in the tolerability of nimodipine. There was no evidence of any significant change in the steady-state pharmacokinetics of nimodipine during five days of combined treatment with 30 mg t.i.d. nimodipine and ranitidine 300 mg/d given as single morning dose to twelve healthy, elderly subjects. Analysis of haemodynamics, clinical chemistry and tolerance also did not reveal any difference between the two treatment periods.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Ipsapirone ; CRF ; ACTH ; cortisol ; time series analysis ; hypothalamic-pituitary-adrenal axis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The neuroendocrine effects (changes in plasma CRF, ACTH and cortisol) of single and multiple (t.d.s. for 2 days) doses of ipsapirone (BAY Q 7821) 5 and 10 mg have been investigated in 6 healthy male volunteers. The study followed a balanced complete block, placebo-controlled and double blind design with two baseline phases (pre and post-treatment). Volunteers were investigated on identical days during 5 successive weeks. The results do not show a specific effect of ipsapirone on the hypothalamic-pituitary-adrenal axis when doses in the range of 5–30 mg per day were given.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 273 (1983), S. 319-326 
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 522 (1988), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naturwissenschaften 64 (1977), S. 535-536 
    ISSN: 1432-1904
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical microbiology & infectious diseases 3 (1984), S. 355-359 
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of ciprofloxacin (Bay o 9867) was examined after a single oral dose of 250 mg and a single intravenous dose of 100 mg respectively in six healthy male volunteers in an open, randomized crossover study. Although ciprofloxacin concentrations were measured in serum, plasma and urine by HPLC with fluorimetric detection and by microbiological assay, all pharmacokinetic calculations are based on the highly sensitive HPLC method only. The mean serum concentration of ciprofloxacin peaked approximately1 h after the oral dose (0.94 mg/l). The elimination half-life was about 4 h and the renal clearance was 4.75 ml/min·kg; both were independent of the route of administration. The total clearance (9.62 ml/min·kg) was about twofold higher than the renal clearance. The volume of distribution of the central compartment was calculated to be 0.16 l/kg and the total volume at steady state was 2.0 l/kg. About 27 % of the oral dose was excreted in urine, whereas the urinary recovery of the i.v. dose was 46 %. The absolute bioavailability of ciprofloxacin was found to be approximately 60 %. Ciprofloxacin appears to follow first-order, three compartment model kinetics.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In einer dreifachen Cross-over-Studie wurden Ciprofloxacin, Norfloxacin und Ofloxacin oral in einer Dosis von 200 mg an sechs Probanden verabreicht, um die Kinetik dieser Präparate in Relation zur bakteriziden Wirkung in Serum und Urin zu untersuchen. Die Serumkonzentrationen für Ciprofloxacin waren ähnlich denen von Norfloxacin und niedriger als mit Ofloxacin. Trotzdem zeigte Ciprofloxacin die höchsten bakteriziden Titer im Serum — als Testorganismus wurdeEscherichia coli C14 verwendet — im Vergleich zu Norfloxacin oder Ofloxacin, die etwa gleich wirksam waren. Diese Ergebnisse zeigen eine gute Korrelation mit Beobachtungen bei Abtötungskurven in menschlichem Vollblut, wobei Ciprofloxacin eine überlegene bakterizide Wirkung zeigte im Vergleich zu Norfloxacin oder Ofloxacin. Die im Urin innerhalb 48 Stunden ausgeschiedenen Mengen an unveränderter Substanz betrugen 35%, 24% und 77% entsprechend für Ciprofloxacin, Norfloxacin und Ofloxacin, was auf ein unterschiedliches Ausscheidungsverhalten von Ofloxacin hinweist. Die Urinmengen in den einzelnen Sammelperioden lagen für alle drei Präparate in vergleichbaren Größenordnungen. Die mittleren Urinkonzentrationen waren für Ciprofloxacin in der 0–4-Stunden-Sammelperiode höher als für Norfloxacin oder Ofloxacin, während Ofloxacin über einen längeren Zeitraum im Urin ausgeschieden wurde. Die Messungen der bakteriziden Wirkung im Urin zeigen, daß Ciprofloxacin in den frühen Sammelperioden die höchsten Titer aufweist, während die längere Ausscheidung von Ofloxacin nicht zu höheren bakteriziden Titern führte im Vergleich zu Ciprofloxacin.
    Notes: Summary A 200 mg oral dose of ciprofloxacin, norfloxacin or ofloxacin was administered to six healthy male volunteers in a three way cross-over study in order to examine the kinetics in humans in relation to the bactericidal activity in serum and urine. Serum concentrations for ciprofloxacin were similar to norfloxacin and lower than ofloxacin. Despite this fact, ciprofloxacin showed the highest serum bactericidal titers compared to norfloxacin and ofloxacin when serum-resistantEscherichia coli C14 was used as a test organism. These results correlate with observations from timekill curve studies in human whole blood, where ciprofloxacin showed superior bactericidal activity compared to norfloxacin or ofloxacin. The amounts of unchanged drug excreted in urine (48 h period) were found to be 35%, 24% and 77% for ciprofloxacin, norfloxacin and ofloxacin respectively, indicating different excretion kinetics. The volumes of urine excreted in the different collection periods were comparable for the three drugs tested. Mean urine concentrations for ciprofloxacin were higher during the 0 to 4 h collection periods, whereas ofloxacin was excreted into the urine over a longer time period. Measurements of urine bactericidal activity showed that ciprofloxacin hat the highest titers during the early collection periods, whereas the prolonged excretion of ofloxacin did not result in higher urine bactericidal titers, compared to ciprofloxacin.
    Type of Medium: Electronic Resource
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