The effects of rifampicin on the pharmacokinetics and pharmacodynamics of orally administered nilvadipine to healthy subjects

Abstract

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 6β-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 μg l-1 h (mean difference - 16.8 μg l-1 h, 95% CI - 9.4, 24.2 μg 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.