title: Pharmacokinetic and Bioequivalence Studies of a Newly Developed Branded Generic of Candesartan Cilexetil Tablets in Healthy Volunteers.
abstract: 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 Cmaxand 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 Cmax, AUC0-t, and AUC0-∞of candesartan were investigated together with safety and tolerability. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for candesartan, Cmax, AUC0-t, and AUC0-∞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 Cmaxwas above (133%) the upper limit of 125% for bioequivalence. Test formulation 2 was found to be bioequivalent and met internationally acceptable regulatory requirements.
authors.affiliation: GlaxoSmithKline, Brentford, Middlesex, UK.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Patel
authors.affiliation: GlaxoSmithKline, Uxbridge, Middlesex, UK.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Palmer
authors.affiliation: GlaxoSmithKline QSI, Bangalore, India.
authors.forename: Shashidhar
authors.initials: S
authors.lastname: Joshi
authors.affiliation: Laboratorios Phoenix S.A.I.C.F., Malvinas Argentinas, Provincia de Buenos Aires, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Di Ció Gimena
authors.affiliation: Laboratorios Phoenix S.A.I.C.F., Malvinas Argentinas, Provincia de Buenos Aires, Argentina.
authors.forename: Florencia
authors.initials: F
authors.lastname: Esquivel
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D016568:Drugs, Generic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011897:Random Allocation; D013607:Tablets; D013777:Tetrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D016568:Drugs, Generic; D013607:Tablets; D013777:Tetrazoles; C077793:candesartan cilexetil
keywords: bioequivalence; branded generic; candesartan; formulation; innovator