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

摘要

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), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were tested for bioequivalence after logarithmic transformation of data and ratios of tmax 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 Cmax and 1.03 (0.99-1.08) for Cmax/AUC(0-infinity). The 90% CI for tmax 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 Cmax and 0.97 (0.90-1.04) for Cmax/AUC(0-infinity). The 90% CI for tmax was 1.00-1.41. All parameters showed bioequivalence between both formulations except for tmax. 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.