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Prevalence of CYP 2C19 alleles, pharmacokinetic and pharmacodynamic variation of clopidogrel and prasugrel in Bangladeshi population
Author(s) -
Bin Sayeed Muhammad Shahdaat,
Hasan Apu Mohd Nazmul,
Munir Maliha Tabassum,
Ahmed Maizbha Uddin,
Islam Mohammad Safiqul,
Haq M Maksumul,
Ahsan Chowdhury H,
Rashid M A,
Shin Jae Gook,
Hasnat Abul
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12390
Subject(s) - clopidogrel , prasugrel , cyp2c19 , genotyping , genotype , medicine , p2y12 , population , pharmacology , pharmacodynamics , allele , pharmacokinetics , biology , genetics , cytochrome p450 , aspirin , gene , environmental health , metabolism
Summary The extent to which cytochrome P450 ( CYP ) 2C19 genotype influences the effectiveness of clopidogrel remains uncertain due to considerable heterogeneity between studies. We used the polymerase chain reaction restriction fragment length polymorphism ( PCR ‐ RFLP ) method for genotyping loss of function ( LOF ) allele, CYP 2C19*2 and gain of function ( GOF ) allele, CYP 2C19*17 in 163 patients undergoing PCI and 165 healthy volunteers from an ethnically distinctive Bangladeshi population. Thirty‐eight patients took prasugrel and 125 patients took clopidogrel among whom 30 patients had their clopidogrel active metabolites ( CAM ) determined by LC ‐ MS / MS 1–1.5 h after clopidogrel intake. All patients who underwent PCI had their P2Y12 per cent inhibition ( PRI ) measured by VerifyNow System. The impact of different genotypes on CAM and PRI were also determined. We did not find significant variation of CYP 2C19*2 ( P > 0.05) and CYP 2C9*17 ( P > 0.05) alleles among healthy volunteers and patients. CAM concentration as well as PRI by clopidogrel varied significantly ( P < 0.05) based on genotypic variation of CYP 2C19*2 and CYP 2C19*17 individually. Such influence was not observed in case of prasugrel. Genotypic variation did not impact PRI but as a whole PRI by prasugrel was better than that of clopidogrel ( P < 0.05). Due to presence of both of alleles the effect on PRI by clopidogrel could not be predicted, effectively indicating possible involvement of other factors. Genotype guided clopidogrel dose adjustment would be beneficial and therefore we propose mandatory genotyping before clopidogrel dosing. Prasugrel proved to be less affected by genotypic variability, but due to lack of sufficient long‐term toxicity data, caution would be adopted before substituting clopidogrel.