Evaluation of the bioequivalence of two tablet formulations of enalapril/hydrochlorothiazide after single oral administration to healthy volunteers.
The pharmacokinetic parameters of two oral formulations of 20/12.5 mg tablets of enalapril/hydrochlorothiazide (CAS 75847-73-3 and CAS 58-93-5, respectively; Penopril as test and another commercially available preparation as reference) were compared in an open-label randomized single oral dose two-period cross-over design to 24 healthy volunteers under fasting conditions. Plasma concentrations of enalaprilat (CAS 76420-72-9), the pharmacologically active metabolite of enalapril, and hydrochlorothiazide were determined by a validated GC/MS and HPLC assay, respectively. Serial blood samples were collected prior to each administration and at 19 timepoints within 36 h after dosing. The parametric 90% confidence intervals of the geometric mean values of the test/reference ratios for enalaprilat were 99.3% to 118.9% (point estimate: 108.7%) for AUC(0-infinity), 97.3% to 116.9% (point estimate: 106.7%) for AUC(0-t), and 92.5% to 113.0% (point estimate: 102.3%) for Cmax, and for hydrochlorothiazide 92.3% to 105.1% (point estimate: 98.5%) for AUC(0-infinity), 92.7% to 105.4% (point estimate: 98.9%) for AUC(0-t), and 97.6% to 115.3% (point estimate: 106.0%) for Cmax, within the acceptance criteria for bioequivalence (80%-125%). Tmax values were analyzed by the nonparametric Wilcoxon test and the difference was not statistically significant. Therefore, it is concluded that the test and reference enalapril/hydrochlorothiazide formulations are bioequivalent for both the extent and the rate of absorption.
Niopas
Ioannis
I
Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece. niopas@pharm.auth.gr
Daftsios
Athanasios C
AC
Nikolaidis
Nicolaos
N
D000328:Adult; D000959:Antihypertensive Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004338:Drug Combinations; D004562:Electrocardiography / Q000187:drug effects; D004656:Enalapril / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency
D000959:Antihypertensive Agents; D004338:Drug Combinations; D006852:Hydrochlorothiazide; D004656:Enalapril