Pharmacokinetics and bioequivalence study of the two 20-MG quinapril hydrochloride tablet formulations in healthy Thai male volunteers

Abstract

Objective: To determine the pharmacokinetics and bioequivalence of two 20-mg quinapril hydrochloride tablet preparations; Quinaril® (The Biolab Ltd, Bangkok, Thailand) as the test and Accupril® as the reference. Material and Method: The present study was a single dose, randomized, two-period crossover design conducted in 24 healthy volunteers under fasting conditions with a 7-day washout period. Serial plasma concentrations of quinapril and its active metabolite quinaprilat up to 24 h after dosing were determined by HPLC with UV detection. The pharmacokinetic parameters were analyzed by noncompartmental analysis and the ANOVA was carried out using logarithmically transformed data of the AUC and Cmax as well as untransformed T max. Results: There were no significant differences between the two preparations regarding the Tmax of quinapril and quinaprilat and their median Tmax were 0.5 h and 1.4 - 1.5 h, respectively. The half-life of quinapril (1.2 h) was faster than quinaprilat (1.8-1.9 h) although the volume of distribution (Vd/F) of quinapril (1.1 L/kg) was larger than quinaprilat (0.3 L/kg), however, its clearance rate (CL/F) was faster when compared to quinaprilat (20-26 ml/min/kg vs. 1.7 ml/min/kg). The mean (90% CI) for the ratios Test/Reference of quinapril were 0.99 (0.89-1.10), 0.99 (0.90-1.09) and 1.01 (0.90-1.14), respectively for AUC0-24, AUC 0-∞ and Cmax. Similarly, the corresponding values for quinaprilat were 0.95 (0.90-1.01), 0.95 (0.90-1.01) and 1.03 (1.00-1.07), respectively. These values were within the bioequivalence range of 0.80 - 1.25, thus, demonstrated the bioequivalence of the two preparations. Conclusion: The results of the present study indicated that the two quinapril HCL preparations are bioequivalent and it can be assumed that they are therapeutically equivalent and exchangeable in clinical practice.