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

Abstract

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.

Pharmacokinetic-pharmacodynamic model of the antihypertensive interaction between telmisartan and hydrochlorothiazide in spontaneously hypertensive rats

“…For the rats used in the pharmacokinetic study, 100‐μl blood samples were drawn from the tail vein at the same time points (0, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 h) after oral administration as described for the pharmacodynamic studies to determine the plasma drug concentration. The concentrations of telmisartan and hydrochlorothiazide were measured according to modified procedures from previous reports [11–14]…”

The application of mass spectrometry in pharmacokinetics studies

“…For example, in one study group 20 healthy male volunteers were dosed with one of two oral formulations of 20/12.5 mg tablets of enalapril/hydrochlorothiazide and multiple plasma samples were collected over the following 96 hours. Drug bioavailability was evaluated on the basis of plasma concentrations of enalapril and its main active metabolite, enalaprilat and hydrochlorothiazide by assaying plasma samples for these three compounds using a LC/MS [35].…”

In-Vitro and in-Vivo Characterization of Mouth Dissolving Tablet: An Updated Review

“…3 However, tablets are most favorite and popular among the currently used dosage forms and efficacy of these dosage forms have been clinically evaluated because of its convenience in terms of self medication, compactness, ease in manufacturing, pain avoidance, and versatility. [4][5][6][7] It has been reported that Dysphagia (difficulty in swallowing) is common among all age groups and more specific with pediatric, geriatric population along with institutionalized patients and patients with nausea, vomiting, and motion sickness complications. 8,9 To avert the problems associated with conventional dosage forms, MDTs have been developed, which combine hardness, dosage uniformity, stability and other parameters, with extremely easy administration, since no water is required for swallowing the tablets and they are thus suitable for geriatric, pediatric and travelling patients.…”