Investigation of a potential pharmacokinetic interaction between perindopril arginine and amlodipine when administered as a single perindopril/amlodipine fixed-dose combination tablet in healthy Chinese male volunteers.

OBJECTIVES To determine whether a potential pharmacokinetic interaction exists between perindopril arginine 5 mg and amlodipine 5 mg, after administration as a fixed-combination of perindopril 5 mg/amlodipine 5 mg (S05985). METHODS A total of 30 subjects was enrolled into this single center, open-label, randomized, 3-period cross-over study and was randomized to receive 1 tablet of S05985, 1 tablet of perindopril tert-butylamine 4 mg, or 1 tablet of amlodipine 5 mg. The doses of both perindopril salts correspond to 3.34 mg of perindopril expressed as free acid. Serial blood samples were collected in each treatment period for determination of plasma amlodipine, perindopril, and perindoprilat concentrations and for calculation of the respective pharmacokinetic parameters (AUC(0-∞), AUC(0-t), C(max), and t(max)). Statistical analyses of the pharmacokinetic parameters included ANOVA and calculations of 90% confidence intervals for the ratio of the geometric means for Cmax, AUC(0-t), and AUC(0-∞). Safety was also assessed. RESULTS A total of 29 subjects completed the study per protocol. There was no serious adverse event. All 90% confidence intervals for C(max), AUC(0-t), and AUC(0-∞) for perindopril, perindoprilat, and amlodipine were within the limits (80.00 - 125%), indicating that both treatments were bioequivalent. CONCLUSION These results indicate that no drug-drug interaction exists after single-dose oral administration of S05985 (perindopril 5 mg and amlodipine 5 mg) when compared to single-dose administration of each component alone, i.e., perindopril tert-butylamine 4 mg and amlodipine 5 mg, given separately.