Comparative bioavailability of two immediate release tablets of enalapril/hydrochlorothiazide in healthy volunteers.
A bioequivalence study of two oral formulations of 20/12.5 mg tablets of enalapril/hydrochlorothiazide was carried out in 20 healthy male volunteers according to a single dose, two-sequence, crossover randomized design. One washout period of nine days was observed between the two periods. Multiple samples were collected over 96 hours post-dosing. Bioavailability was evaluated on the basis of plasma concentrations of enalapril and its main active metabolite, enalaprilat and hydrochlorothiazide. Plasma samples were assayed for enalapril, enalaprilat and hydrochlorothiazide using a selective and sensitive high-performance liquid chromatography method with mass spectrometry detection (LC-MS). The pharmacokinetic parameter values of Cmax and tmax were obtained directly from plasma data, k(e) was estimated by log-linear regression, and AUC was calculated by trapezoidal rule. Different statistical tests were performed on the basis of untransformed and log-transformed data and the overall residual variance from ANOVA. Assuming the accepted tolerance intervals, a beta-error of 20% and 90% confidence intervals (alpha = 0.10), all the generally accepted tests (Schuirmann test and Wilcoxon-Tukey and Hauschke nonparametric tests) showed that the formulations can be considered as bioequivalent with respect to the extent of absorption, given by the AUC(0-infinity) and with respect to rate of absorption as assessed by Cmax and tmax.
Maya
Manuela T
MT
Centro de Metabolismos e Genética, Faculdade de Farmácia da Universidade de Lisboa, Portugal.
Goncalves
Nuno J
NJ
Silva
Nuno E
NE
Filipe
Augusto E P
AE
Morais
José A
JA
Caturla
M C
MC
Rovira
M
M
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004656:Enalapril / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D006852:Hydrochlorothiazide / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D018709:Statistics, Nonparametric; D013607:Tablets
D013607:Tablets; D006852:Hydrochlorothiazide; D004656:Enalapril