BIOEQUIVALENCE STUDIES OF TWO IRANIAN GENERIC FORMULATIONS OF CAPTOPRIL IN HEALTHY VOLUNTEERS

Background and Objective – Captopril is a widely used antihypertensive drug and is formulated by several pharmaceutical companies in Iran. This study was conducted to compare the bioavailability of two captopril formulations with reference products of the same strength in healthy volunteers. Methods – The relative bioavailability of captopril was determined in two single-blind, single dose, randomized, crossover, two-phase studies. The relative bioavailability of the test product (first study: generic captopril 25 mg tablets; second study: generic captopril 50 mg tablets) with respect to the reference product (first study: Capoten® 25 mg tablets; second study: Capoten® 50 mg tablets, Bristol-Myers Squibb) was determined. Twelve healthy volunteers in two groups took part in these studies and took either the test or reference tablets in the first phase and received the other tablet in the second phase of each study. Results – In the first study, the mean values for the variable peak plasma concentration (Cmax) were 459.8 ng/mL for the reference and 466.6 ng/mL for the test product. The mean values for the variable area under the curve (AUC0-t) were 1392.5 ng.hr/mL and 1403.2 ng.hr/mL for the reference and test product, respectively. In the second study, the mean values for the variable Cmax were 535.5 ng/mL for the reference and 517.2 ng/mL for the test product. The mean values for the variable AUC0-t were 1518.8 ng.hr/mL and 1444.5 ng.hr/mL for the reference and test product, respectively. The 90% confidence intervals for the test/reference mean ratios of Cmax and AUC0-t were between 0.90 and 1.19, which is within the conventional bioequivalence range of 80 – 125%. Conclusion – The test products were bioequivalent to the reference (Capoten®) in terms of the rate and extent of absorption of captopril in both 25 mg and 50 mg strengths.