Pharmacokinetic Equivalence Study of 2 Formulations of Perindopril Tert-Butylamine Tablets

Abstract Objective The present study was conducted to compare the bioavailability of 2 formulations of a 4-mg perindopril tert-butylamine tablet (test and reference formulations). Methods This was a randomized, single-blind, 2-period, 2-sequence crossover study involving 18 healthy adult male and female subjects under fasting conditions. A single dose of the test or reference product was administered in each of the 2 study periods, separated by a 3-week washout period. The pharmacokinetic parameters, including area under the plasma concentration–time curve from time zero to 192 hours (AUC0–192 ), AUC0–∞ , Cmax , Tmax , and t½ , were determined based on the concentrations of the perindopril parent compound and its metabolite (perindoprilat) by using an HPLC-MS/MS detector. Results The geometric mean ratios (90% CIs) of the test drug/reference drug for the perindopril parent compound were 106.41% (99.02–114.35) for AUC0–192 , 106.38% (99.08–114.22) for AUC0–∞ , and 110.15% (98.57–123.10) for Cmax ; for perindoprilat, these values were 104.15% (97.32–111.44), 100.13% (89.87–111.57), and 103.85% (92.20–116.97), respectively. They were all within the acceptance range for bioequivalence (80%–125%). Tmax values for the test and reference drugs were not significantly different ( P > 0.05) for the perindopril parent compound but were significantly different ( P ≤ 0.05) for perindoprilat. No dropouts or adverse events were reported. Conclusions It was concluded that the 2 formulations of the perindopril tablets studied are bioequivalent.