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

Arzneimittelforschung. 2008;58(8):369-75. doi: 10.1055/s-0031-1296523.


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 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 Cmax 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 Cmax 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 Cmax, 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 Cmax, 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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / blood
  • Antihypertensive Agents / pharmacokinetics*
  • Area Under Curve
  • Calibration
  • Chemistry, Pharmaceutical
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Combinations
  • Half-Life
  • Humans
  • Hydrochlorothiazide / administration & dosage*
  • Hydrochlorothiazide / blood
  • Hydrochlorothiazide / pharmacokinetics*
  • Losartan / administration & dosage*
  • Losartan / blood
  • Losartan / pharmacokinetics*
  • Male
  • Middle Aged
  • Tablets, Enteric-Coated
  • Therapeutic Equivalency


  • Antihypertensive Agents
  • Drug Combinations
  • Tablets, Enteric-Coated
  • Hydrochlorothiazide
  • Losartan