Bio equivalence Study of Two Different Film-coated Tablet Formulations of Losartan-Hydrochlorothiazide in Healthy Volunteers

Abstract

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 (CAS 58-93-5). Seventy-three healthy subjects were enrolled in arandomised, 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.

Key words

Antihypertensive drugs - CAS 58-93-5 - CAS 124750-99-8 - Hydrochlorothiazide, bioequivalence - Losartan, bioequivalence

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