Comparative bioavailability of two immediate-release tablets of lisinopril/hydrochlorothiazide in healthy volunteers

Aim: Two formulations of lisinopril/hydrochlorothiazide (20 mg/12.5 mg) were evaluated for bioequivalence after single dosing in healthy volunteers. Methods: The study was conducted according to an open, randomized, 2-period crossover design with a 2-week washout interval between doses. Twenty-four volunteers participated and all completed the study successfully. Lisinopril and hydrochlorothiazide were determined in plasma by HPLC. The pharmacokinetic parameters AUC(0-t), AuC0-infinity, C-max and C-max/AUC(0-infinity) were tested for bioequivalence after logarithmic transformation of data and ratios of t(max) were evaluated non-parametrically. Results: For lisinopril, the parametric analysis revealed the following test/reference ratios and their confidence intervals (90% CI): 1.01 (0.84 - 1.22) for AUC(0-t), 0.98 (0.81 - 1.19) for AUC(0-infinity), 1.02 (0.83 - 1.25) for C-max and 1.03 (0.99 - 1.08) for C-max/AUC(0-infinity). The 90% CI for t(max) was 0.94 - 1.07. All parameters showed bioequivalence between both formulations. As for hydrochlorothiazide, test/reference ratios and their confidence intervals (90% CI) were: 1.05 (0.95 - 1.17), 1.02 (0.93 - 1.12) for AUC(0-infinity), 0.99 (0.89 - 1.07) for C-max, and 0.97 (0.90 - 1.04) for C-max/AUC(0-infinity). The 90% CI for t(max) was 1.00 - 1.41. All parameters showed bioequivalence between both formulations except for t(max). A discrete fall in both systolic (SBP) and diastolic (DBP) blood pressure was observed after drug administration. The time course of both parameters was similar for the 2 formulations. Heart rates also followed a similar time profile. Conclusions: The bioequivalence of the 2 formulations of lisinopril/hydrochlorothiazide was demonstrated.