Acta Pharmaceutica, Vol. 64 No. 1, 2014.
Original scientific paper
https://doi.org/10.2478/acph-2014-0001
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
NINA BRVAR
; Krka, d.d., 8501 Novo mesto, Slovenia
SYLVAIN LACHANCE
; inVentiv Health Clinical, Québec, Québec, Canada
ANN LÉVESQUE
; inVentiv Health Clinical, Québec, Québec, Canada
MARJANCA BREZNIK
; Krka, d.d., 8501 Novo mesto, Slovenia
LEA CVITKOVIČ-MARIČIČ
; Krka, d.d., 8501 Novo mesto, Slovenia
MATEJA MERSLAVIČ
; Krka, d.d., 8501 Novo mesto, Slovenia
IZTOK GRABNAR
; University of Ljubljana, Faculty of Pharmacy, 1000 Ljubljana, Slovenia
TATJANA MATEOVIĆ-ROJNIK
; Krka, d.d., 8501 Novo mesto, Slovenia
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.
Keywords
bioavailability; food effect; clopidogrel; clopidogrel carboxylic acid
Hrčak ID:
113579
URI
Publication date:
31.3.2014.
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