title: Effect of Nifedipine on the Steady-State Pharmacokinetics and Pharmacodynamics of Irbesartan in Healthy Subjects.
abstract: BACKGROUND: In clinical practice, nifedipine has the potential to alter the pharmacokinetics, and therefore possibly the pharmacodynamics and efficacy or safety, of irbesartan. The objectives of the current study were to determine the effects of concomitant administration of nifedipine on the steady-state pharmacokinetics and pharmacodynamics of irbesartan in 12 healthy subjects. METHODS AND RESULTS: This was an open-label, randomized, crossover study. Each subject received irbesartan 300 mg once daily for 4 days in one period and irbesartan 300 mg once daily plus long-acting nifedipine (Procardia XL, Pratt Pharmaceuticals, New York, NY) 30 mg once daily for 4 days in the other period. The order of treatment periods was randomized, and a minimum 7-day washout phase separated the two periods. Steady state was achieved by day 3. On day 4, no significant differences were observed between the two treatments with respect to maximum concentration of irbesartan at the end of the dosing interval (C(max)) or the area under the plasma concentration versus time curve during a dosing interval (AUC(tau)) of irbesartan. Steady-state C(max) and AUC(tau) met the criteria for bioequivalence when irbesartan was administered alone or with nifedipine. On day 4, mean plasma renin activity was somewhat higher at every point but one when irbesartan was administered with nifedipine; however, no significant difference was observed between the two treatments in mean 24-hour AUC values. On day 4, there was a modest overall decrease from baseline in mean blood pressure for both treatments. No significant differences were observed between the two treatments in mean 24-hour AUC values for seated diastolic or systolic blood pressure. No serious adverse events were reported. CONCLUSIONS: Concomitant administration of nifedipine 30 mg with irbesartan 300 mg for 4 days in healthy subjects (1) does not alter the steady-state pharmacokinetic parameters of irbesartan, (2) results in C(max) and AUC(tau) values for irbesartan that meet the criteria for bioequivalence, and (3) is well tolerated.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, USA
authors.initials: MR
authors.lastname: Marino
authors.initials: JL
authors.lastname: Hammett
authors.initials: I
authors.lastname: Ferreira
authors.initials: NF
authors.lastname: Ford
authors.initials: HD
authors.lastname: Uderman