Pharmacokinetic properties and bioequivalence of candesartan cilexetil in Korean healthy volunteers

Abstract

Candesartan is a long-acting and selective nonpeptide AT1 subtype angiotensin II receptor antagonist. The aim of this study was to compare the pharmacokinetics and to evaluate the bioequivalence of two candesartan cilexetil 16 mg formulations. Forty healthy volunteers were randomly assigned into two groups. After a single dose of 16 mg candesartan cilexetil oral administration, blood samples were collected at specific time intervals from 0–36 h. The plasma concentrations of candesartan cilexetil were determined by LC-MS/MS. The pharmacokinetic parameters such as AUClast, AUCinf and Cmax were calculated and the 90% confidence intervals of the ratio (test/reference) pharmacokinetic parameters were obtained by analysis of variance on logarithmically transformed data. The mean for AUClast in the reference and the test drug were 1530.1 ± 434.6 and 1315.7 ± 368.6 ng·h/mL. The mean for AUCinf in the reference and the test drug were 1670.0 ± 454.5 and 1441.2 ± 397.8 ng·h/mL. The mean value for Cmax in the reference and the test drug was 142.6 ± 41.0 and 134.9 ± 41.4 ng/mL. The 90% confidence intervals for the AUClast, AUCinf and Cmax were in the range of log 0.81–log 0.91, log 0.81–log 0.91 and log 0.88–log1.01, respectively. No adverse events were reported by subjects or found on analysis of vital signs or laboratory tests. This single dose study found that the test and reference products met the regulatory criteria for bioequivalence in these health volunteers. Both formulations were safe and well tolerated in 16 mg of candesartan cilexetil hydrochloride.