التفاصيل البيبلوغرافية
| العنوان: |
Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide. |
| المؤلفون: |
von Richter, Oliver, Lahu, Gezim, Huennemeyer, Andreas, Herzog, Rolf, Zech, Karl, Hermann, Robert |
| المصدر: |
Clinical Pharmacokinetics; 2007, Vol. 46 Issue 7, p613-622, 10p |
| مصطلحات موضوعية: |
ENZYME inhibitors, HYDROCARBON metabolism, AMINES, AMINOPYRIDINES, BENZAMIDE, CLINICAL trials, COMPARATIVE studies, CROSSOVER trials, ESTERASES, HYDROCARBONS, RESEARCH methodology, MEDICAL cooperation, ORAL drug administration, OXIDOREDUCTASES, PHARMACOKINETICS, RESEARCH, DRUG tablets, TIME, TRANQUILIZING drugs, EVALUATION research, PHOSPHODIESTERASE inhibitors, CHEMICAL inhibitors |
| مستخلص: |
Objective: To investigate the effects of steady-state dosing of fluvoxamine, an inhibitor of cytochrome P450 (CYP) 1A2 and CYP2C19, on the pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4 (PDE4) inhibitor and its pharmacodynamically active metabolite roflumilast N-oxide.Methods: In an open-label, non-randomised, one-sequence, two-period, two-treatment crossover study, 14 healthy subjects received a single oral dose of roflumilast 500 microg on study day 1. After a 6-day washout period, repeated doses of fluvoxamine 50 mg once daily were given from days 8 to 21. On day 15, roflumilast 500 microg and fluvoxamine 50 mg were taken concomitantly. Percentage ratios of test/reference (reference: roflumilast alone; test: roflumilast plus steady-state fluvoxamine) of geometric means and their 90% confidence intervals for area under the plasma concentration-time curve, maximum plasma concentration (roflumilast and roflumilast N-oxide) and plasma clearance of roflumilast were calculated.Results: Upon co-administration with steady-state fluvoxamine, the exposure to roflumilast as well as roflumilast N-oxide increased by a factor of 2.6 and 1.5, respectively. Roflumilast plasma clearance decreased by a factor of 2.6, from 9.06 L/h (reference) to 3.53 L/h (test). The combined effect of fluvoxamine co-administration on roflumilast and roflumilast N-oxide exposures resulted in a moderate (i.e. 59%) increase in total PDE4 inhibitory activity.Conclusion: Co-administration of roflumilast and fluvoxamine affects the disposition of roflumilast and its active metabolite roflumilast N-oxide most likely via a potent dual pathway inhibition of CYP1A2 and CYP2C19 by fluvoxamine. The exposure increases observed for roflumilast N-oxide are suggested to be attributable to CYP2C19 co-inhibition by fluvoxamine and thus, are not to be expected to occur when roflumilast is co-administered with more selective CYP1A2 inhibitors. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
