Bioequivalence study of two different film-coated tablet formulations of losart-an-hydrochlorothiazide in healthy volunteers

The study was conducted in order to assess the bioequivalence of two film-coated formulations containing 100 mg of losartan (CAS 124750-99-8) and 12.5 mg of hydrochlorothiazide (CAS58-93-5). Seventy-three healthy subjects were enrolled in a randomised, single-dose, open-label, two-way crossover study, with a minimum washout period (of 7 days. A total of 21 blood samples were collected up to 36 h post-dosing. Losartan, losartan carboxy acid and hydrochlorothiazide levels were determined by liquid chromatography with tandem mass detection (lower limit of quantification: 1.01 ng/mL for hydrochlorothiazide, 2.02 ng/mL for losartan and 2.51 ng/mL for losartan carboxy acid). Pharmacokinetic parameters used for bioequivalence assessment (AUC(0-t) and C-max as primary and AUC(0-Inf) as secondary pharmacokinetic parameters) were determined from the losartan and hydrochlorothiazide concentration data using non-compartmental analysis. Data from losartan carboxy acid was reported and presented as supportive data. The 90 % confidence intervals (obtained by ANOVA) for losartan were 97.05-118.48 % for C-max, 100.76-106. 10 % for AUC(0-t) and 100.80-106.10 % for AUC(0-inf) whereas for hydrochlorothiazide the 90 % confidence intervals obtained were 103.94-115.33 % for C-max, 101.97-109.61 % for AUC(0-t) and 101.77-109.02 % for AUC(0-inf), and for losartan carboxy acid the intervals obtained were 98.31-107.82 % for C-max, 97.89-104.30 % for AUC(0-t) and 98.06-104.30 % for AUC(0-inf). All the 90 % confidence intervals obtained for all the parameters assessed were within the predefined ranges (80-125%). Based on these results, it can be concluded that the evaluated formulations are bioequivalent in terms of rate and extent of absorption.