Potential pharmacokinetic interactions in fixed-dose combinations of perindopril/indapamide/amlodipine compared with perindopril/indapamide and amlodipine in healthy Chinese volunteers

Abstract

S05590 is a fixed-dose combination of perindopril tert-butylamine 4 mg/indapamide 1.25 mg, and S06593 is a fixed-dose combination of perindopril arginine 5 mg/indapamide 1.25 mg/amlodipine 5 mg. The purpose of this study was to determine whether pharmacokinetic interactions exist among the components of S06593, compared with S05590 and amlodipine as reference drugs, in healthy Chinese male volunteers after a single oral administration under fasting conditions. A single-center, open-label, randomized, three-period, six-way crossover study was conducted. A total of 42 participants were enrolled and randomized to receive S05590 plus amlodipine, or S06593. The doses of perindopril were 3.34 mg in both S05590 and S06593, calculated as free acid. Blood samples were collected in each treatment period to determine the plasma concentrations of perindopril, indapamide and amlodipine, as well as perindoprilat, the main metabolite of perindopril. A total of 39 participants completed this study. The 90% confidence intervals of the geometric mean ratios of Cmax, AUC0-t and AUC0-∞ for perindopril, perindoprilat, indapamide and amlodipine were all within 80.00–125.00%, thus indicating that S05590 plus amlodipine and S06593 were pharmacokinetically equivalent. During the study, only one serious emergent adverse event was reported, which was deemed not to be associated with the study drug. No serious treatment-associated adverse events were observed.