caa a22 4500 477056296 CHVBK 20180405111347.0 cr unu---uuuuu 170330e19961201xx s 000 0 eng 10.1007/s002280050202 doi (NATIONALLICENCE)springer-10.1007/s002280050202 The single and multiple dose pharmacokinetics of pranlukast in healthy volunteers [Elektronische Daten] [D. R. Brocks, J. W. Upward, P. Georgiou, G. Stelman, E. Doyle, E. Allen, P. Wyld, M. J. Dennis] Objective: The pharmacokinetics of pranlukast, a leukotriene LTD4 antagonist, were studied in 48 young, healthy subjects after single and repeated oral doses (given every 12 h) ranging from 112.5 to 675 mg. The doses were administered 30 minutes after a light breakfast. Results: Maximal drug concentrations generally occurred between 2 and 6 h after dosing, and there was some evidence of an absorption lag-time. Secondary peaks were observed in the plasma concentration vs. time profiles of many of the study subjects after both single and repeated doses, particularly during the period of maximum drug absorption. In general, after both single and repeated doses, there were related increases in the corresponding Cmax and AUC with a rise in dose, although the increase was diminished at doses above 450 mg. With repeated dosing of pranlukast the mean AUC was generally higher (up to 1.6-fold), and the higher plasma concentrations allowed characterisation of a longer mean t1/2 than after single dose administration. The mean steady-state trough plasma concentrations attained after evening doses were considerably higher (up to 14-fold) than those obtained after the morning dose. Conclusion: The data suggested that the pharmacokinetics of pranlukast are influenced by the time of dosing. Based on analysis of urinary 6β-hydroxycortisol excretion, there was no evidence that pranlukast modified the metabolic activity of cytochrome P-450 3A isoenzymes. Springer-Verlag Berlin Heidelberg, 1996 Key words Pranlukast nationallicence Asthma bronchial nationallicence pharmacokinetics nationallicence leukotriene antagonist nationallicence Brocks D. R. College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada S7N 5C9, CA aut Upward J. W. SmithKline Beecham Pharmaceuticals, Department of Clinical Pharmacology, and Statistics, Harlow, Essex, UK, GB aut Georgiou P. SmithKline Beecham Pharmaceuticals, Department of Clinical Pharmacology, and Statistics, Harlow, Essex, UK, GB aut Stelman G. SmithKline Beecham Pharmaceuticals, Department of Drug Metabolism and Pharmacokinetics, King of Prussia, PA, USA, and The Frythe, Welwyn, Herts, UK, RU aut Doyle E. SmithKline Beecham Pharmaceuticals, Department of Drug Metabolism and Pharmacokinetics, King of Prussia, PA, USA, and The Frythe, Welwyn, Herts, UK, RU aut Allen E. SmithKline Beecham Pharmaceuticals, Department of Clinical Pharmacology, and Statistics, Harlow, Essex, UK, GB aut Wyld P. Inveresk Clinical Research Ltd., Riccarton, Edinburgh, UK, GB aut Dennis M. J. SmithKline Beecham Pharmaceuticals, Department of Drug Metabolism and Pharmacokinetics, King of Prussia, PA, USA, and The Frythe, Welwyn, Herts, UK, RU aut https://doi.org/10.1007/s002280050202 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050202 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Brocks D. R. College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada S7N 5C9, CA aut NATIONALLICENCE 700 1- Upward J. W. SmithKline Beecham Pharmaceuticals, Department of Clinical Pharmacology, and Statistics, Harlow, Essex, UK, GB aut NATIONALLICENCE 700 1- Georgiou P. SmithKline Beecham Pharmaceuticals, Department of Clinical Pharmacology, and Statistics, Harlow, Essex, UK, GB aut NATIONALLICENCE 700 1- Stelman G. SmithKline Beecham Pharmaceuticals, Department of Drug Metabolism and Pharmacokinetics, King of Prussia, PA, USA, and The Frythe, Welwyn, Herts, UK, RU aut NATIONALLICENCE 700 1- Doyle E. SmithKline Beecham Pharmaceuticals, Department of Drug Metabolism and Pharmacokinetics, King of Prussia, PA, USA, and The Frythe, Welwyn, Herts, UK, RU aut NATIONALLICENCE 700 1- Allen E. SmithKline Beecham Pharmaceuticals, Department of Clinical Pharmacology, and Statistics, Harlow, Essex, UK, GB aut NATIONALLICENCE 700 1- Wyld P. Inveresk Clinical Research Ltd., Riccarton, Edinburgh, UK, GB aut NATIONALLICENCE 700 1- Dennis M. J. SmithKline Beecham Pharmaceuticals, Department of Drug Metabolism and Pharmacokinetics, King of Prussia, PA, USA, and The Frythe, Welwyn, Herts, UK, RU aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer