期刊
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
卷 53, 期 2, 页码 203-206出版社
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.0306-5251.2001.01545.x
关键词
calcium channel antagonist; CYP3A4; drug interaction; enzyme induction; nilvadipine; rifampicin
Aims To study the effects of rifampicin on the pharmacokinetics and pharmacodynamics of nilvadipine. Methods Five healthy adult volunteers received nilvadipine (4 mg) orally before and after a 6 day treatment with rifampicin. Blood and Urine were collected and assayed for plasma nilvadipine and urinary 6beta-hydroxycortisol and cortisol. Results The treatment with rifampicin reduced the mean (+/-s.d.) AUC of nilvadipine from 17.4 +/- 8.4 to 0.6 +/- 0.4 mug l(-1) h (mean difference -16.8 mug l(-1) h, 95% CI -9.4, 24.2 mug l(-1) h). While the administration of nilvadipine alone elicited a significant (P < 0.05) hypotensive (mean difference for diastolic blood pressure -8 mmHg, 95% CI -4, -12 mmHg) and reflex tachycardia (mean difference 5 beats min(-1), 95% CI 1, 9 beats min(-1)), the treatment with rifampicin abolished these responses. The urinary 6β-hydroxycortisol/cortisol ratio showed a significant (P<0.05) increase from 10.3 +/- 4.0 to 50.3 +/- 24,6 by rifampicin: mean difference 40.1, 95% CI 20.4, 59.8. Conclusions Because rifampicin may greatly decrease the oral bioavailability of nilvadipine, caution is needed when these two drugs are to be coadministered.
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