Bioequivalence Study of Two Losartan Formulations Administered Orally in Healthy Male Volunteers

Abstract

The bioavailability of a new losartan preparation (2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol monopotassium salt, CAS 114798-26-4) was compared with the reference preparation of the drug in 24 healthy male volunteers, aged between 19 and 32. The open, randomized, single-blind two-sequence, two-period crossover study design was performed. Under fasting conditions, each subject received a single oral dose of 100 mg losartan as a test or reference formulation. The plasma concentrations of losartan and its active metabolite were analyzed by a rapid and sensitive HPLC method with UV detection. The pharmacokinetic parameters included AUC0-36h, AUC0-infinity, Cmax, t1/2, and Ke. Values of AUC0-infinity demonstrate nearly identical bioavailability of losartan from the examined formulations. The AUC0-infinity of losartan was 2019.92+/-1002.90 and 2028.58+/-837.45 ng x h/ml for the test and reference formulation, respectively. The AUC0-infinity of the metabolite was 10851.52+/-4438.66 and 11041.18 +/-5015.81 ng x h/ml for test and reference formulation, respectively. The maximum plasma concentration (Cmax) of losartan was 745.94+/-419.75 ng/ml for the test and 745.74+/-329.99 ng/ml for the reference product and the Cmax of the metabolite was 1805.77+/-765.39 and 1606.22 +/-977.22 ng/ml for the test and reference product, respectively. No statistical differences were observed for Cmax and the area under the plasma concentration-time curve for both losartan and its active metabolite. 90 % confidence limits calculated for Cmax and AUC from zero to infinity (AUC0-infinity) of losartan and its metabolite were included in the bioequivalence range (0.8-1.25 for AUC). This study shows that the test formulation is bioequivalent to the reference formulation for losartan and its main active metabolite.