Premium
Pharmacokinetic and Bioequivalence Studies of a Newly Developed Branded Generic of Candesartan Cilexetil Tablets in Healthy Volunteers
Author(s) -
Patel Rajesh,
Palmer Jonathan L.,
Joshi Shashidhar,
Di Ció Gimena Alejandro,
Esquivel Florencia
Publication year - 2016
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.321
Subject(s) - bioequivalence , cmax , medicine , pharmacokinetics , pharmacology , candesartan , crossover study , bioavailability , tolerability , innovator , confidence interval , placebo , adverse effect , angiotensin ii , alternative medicine , pathology , intellectual property , computer science , blood pressure , operating system
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.