title: Pharmacogenetic selection of volunteers increases stringency of bioequivalence studies; the case of clopidogrel.
abstract: Clinical response to clopidogrel varies widely due to under-dosing, drug interactions and intrinsic interindividual differences resulting from genetic polymorphisms. Cytochrome P450-2C19 is the principal enzyme involved in the activation of the prodrug and loss-of-function alleles have been described. Upon expiration of the pharmaceutical patent of clopidogrel, generic manufacturers have started to subject interchangeable formulations to bioequivalence studies. The purpose of the current investigation was to study the effect of selection of volunteers homozygous for the CYP2C19*1 haplotype on the bioavailability of clopidogrel. A regular 2×2 bioequivalence study between two formulations of clopidogrel was performed in volunteers selected and unselected for relevant CYP2C19 haplotypes for the Mexican population. It was found that selection of volunteers homozygous for the CYP2C19*1 haplotype, increased the stringency of bioequivalence statistics and resulted in bioinequivalence of a generic clopidogrel compound that otherwise proved equivalent when tested in an open unselected population. Augmentation of bioequivalence strictness is expected to result from pharmacogenetic selection of volunteers.
authors.affiliation: The Popular Autonomous University of the State of Puebla, Puebla Pue., Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Garcés-Eisele
authors.affiliation: Clinical Laboratories of Puebla of Bioequivalence, Puebla Pue., Mexico ; The Popular Autonomous University of the State of Puebla, Puebla Pue., Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Ruiz-Argüelles
authors.affiliation: Clinical Laboratories of Puebla of Bioequivalence, Puebla Pue., Mexico.
authors.forename: Larisa
authors.initials: L
authors.lastname: Estrada-Marín
authors.affiliation: Clinical Laboratories of Puebla, Puebla Pue., Mexico.
authors.forename: Virginia
authors.initials: V
authors.lastname: Reyes-Núñez
authors.affiliation: Clinical Laboratories of Puebla of Bioequivalence, Puebla Pue., Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Vázquez-Pérez
authors.affiliation: Clinical Laboratories of Puebla of Bioequivalence, Puebla Pue., Mexico.
authors.forename: Olga
authors.initials: O
authors.lastname: Guzmán-García
authors.affiliation: The Popular Autonomous University of the State of Puebla, Puebla Pue., Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Coutiño-Medina
authors.affiliation: Clinical Laboratories of Puebla of Bioequivalence, Puebla Pue., Mexico.
authors.forename: Leticia
authors.initials: L
authors.lastname: Acosta-Sandria
authors.affiliation: Clinical Laboratories of Puebla of Bioequivalence, Puebla Pue., Mexico ; The Popular Autonomous University of the State of Puebla, Puebla Pue., Mexico.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Cedillo-Carvallo
keywords: CYP2C19; Clopidogrel; bioequivalence; pharmacogenetics; pharmacogenomics; polymorphism