Mirtazapine and paroxetine: a drug-drug interaction study in healthy subjects

被引:20
作者
Ruwe, FJL
Smulders, RA
Kleijn, HJ
Hartmans, HLA
Sitsen, JMA
机构
[1] NV Organon, Clin Dev Dept, NL-5340 BH Oss, Netherlands
[2] NV Organon, Dept Drug Metab & Kinet, NL-5340 BH Oss, Netherlands
[3] Kendle Clin Pharmacol Unit, NL-3584 CJ Utrecht, Netherlands
关键词
mirtazapine; paroxetine; cytochrome P-450; drug-drug interaction; pharmacokinetics;
D O I
10.1002/hup.318
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Paroxetine inhibits cytochrome P-450 2D6, which is involved in the metabolism of mirtazapine. The possible drug-drug interaction between two pharmacologically distinct antidepressants, mirtazapine and paroxetine, has been investigated in a randomized, three-way crossover study in 24 healthy male and female subjects. After a titration phase of 3 days, each subject received single daily doses of 30 mg mirtazapine, 40 mg paroxetine or the combination for 6 days. Assessments included serial blood sampling for pharmacokinetics at steady state cognitive testing using the test battery of CDR Ltd, a visual analogue mood rating scale (Bond and Lader) and the Leeds Sleep Evaluation Questionnaire. Paroxetine inhibits the metabolism of mirtazapine, as shown by increases of approximately 17% and 25% of the 24 h AUC's of mirtazapine and its demethyl metabolite, respectively. Mirtazapine did not alter the pharmacokinetics of paroxetine. The combined administration of mirtazapine and paroxetine probably does not alter cognitive functioning or result in major changes on the visual analogue mood rating scale and Sleep Evaluation Questionnaire, compared with the administration of either drug alone. The incidence of adverse events was lower during combined administration of mirtazapine and paroxetine than during administration of either drug alone. Fatigue, dizziness, headache, nausea, anxiety and somnolence were the most common adverse events during combined administration. These data suggest that the combination of mirtazapine and paroxetine is unlikely to lead to clinically relevant drug-drug interactions and can be used without dose adjustment of either drug. The combination may even be better tolerated than either drug alone. Copyright (C) 2001 John Wiley & Sons, Ltd.
引用
收藏
页码:449 / 459
页数:11
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