Pharmacokinetic and Bioequivalence Studies of a Newly Developed Branded Generic of Candesartan Cilexetil Tablets in Healthy Volunteers

Two bioavailability/bioequivalence studies were carried out to evaluate the pharmacokinetics of candesartan cilexetil 16-mg tablet formulations. A pilot study was used to optimize the formulation and manufacturing process prior to conducting the definitive study. The pilot study was a single-dose, randomized, 2-period crossover, and the definitive study was a single-dose, randomized, 3-period, 6-sequence crossover study in healthy adults. In the pilot study the test formulation was 24% and 18% greater for C-max and AUC, respectively, compared with the innovator product. Following optimization two 16-mg candesartan cilexetil tablet formulations were taken forward into the second bioavailability study.Eighteen healthy fasted adult subjects were dosed with either the test formulations or the innovator. The pharmacokinetic parameters C-max, AUC(0-t), and AUC(0-) of candesartan were investigated together with safety and tolerability. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for candesartan, C-max, AUC(0-t), and AUC(0-) were within the boundary of 0.8-1.25 for one of the test formulations (formulation 2). For test formulation 3 the 90%CI of GMR for C-max was above (133%) the upper limit of 125% for bioequivalence. Test formulation 2 was found to be bioequivalent and met internationally acceptable regulatory requirements.