title: Comparative bioavailability of two oral formulations of clopidogrel: determination of clopidogrel and its carboxylic acid metabolite (SR26334) under fasting and fed conditions in healthy subjects.
abstract: Two randomized, single dose, 2-period, 2-sequence crossover studies were conducted to evaluate the comparative bioavailability of two clopidogrel formulations under fasting and fed conditions. Assessment of bioequivalence was based upon measurement of plasma concentrations of the parent drug, clopidogrel, and its major (inactive) metabolite, clopidogrel carboxylic acid, using improved methanol-free extraction. Bioequivalence of Krka's formulation to the innovator's formulation was demonstrated under both fasting and fed conditions on 205 volunteers. Confidence intervals for AUC0-t, AUC0-inf and Cmax of clopidogrel and its main metabolite were well within the acceptance range of 80.00 to 125.00 %. Food substantially increased the bioavailability of clopidogrel from both formulations, while no effect of food on the extent and rate of exposure to the metabolite was observed. The effect of food was comparable between the two formulations, as indicated by the same direction and rank of food impact on the bioavailability of both formulations.
authors.forename: Nina
authors.initials: N
authors.lastname: Brvar
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lachance
authors.forename: Ann
authors.initials: A
authors.lastname: Lévesque
authors.forename: Marjanca
authors.initials: M
authors.lastname: Breznik
authors.forename: Lea
authors.initials: L
authors.lastname: Cvitkovič Marčič
authors.forename: Mateja
authors.initials: M
authors.lastname: Merslavič
authors.forename: Iztok
authors.initials: I
authors.lastname: Grabnar
authors.forename: Tatjana
authors.initials: T
authors.lastname: Mateovič-Rojnik
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D000077144:Clopidogrel; D018592:Cross-Over Studies; D005215:Fasting / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: C521473:SR26334; D000077144:Clopidogrel; D013988:Ticlopidine