Prevalence of CYP2C19 alleles, pharmacokinetic and pharmacodynamic variation of clopidogrel and prasugrel in Bangladeshi population

Abstract

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, CYP2C19*2 and gain of function (GOF) allele, CYP2C19*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 CYP2C19*2 (P > 0.05) and CYP2C9*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 CYP2C19*2 and CYP2C19*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.

Impact of CYP2C19 Polymorphism on Antiplatelet Potency of Prasugrel 5 and 10 mg Daily Maintenance

“…Many studies showed that CYP genetic variants had a significant influence on the pharmacokinetic and pharmacodynamic responses to clopidogrel, causing diminished antiplatelet response [24]. However, prasugrel is believed to be less affected by genotypic variability [25][26][27]. Moreover, one study found no significant difference in pharmacodynamic response for prasugrel 5 or 10 mg [28], what is in disagreement with the index data.…”

Prevalence of NPHS2 gene R229Q polymorphism in Bangladeshi children with nephrotic syndrome

“…3 ml of venous blood was collected from all patients in sterile tubes containing EDTA-Na 2 and stored at -80 C until genomic DNA (gDNA) extraction. gDNA was isolated from blood by previously published method [20]. The quantity and purity of the isolated DNA were assessed by using a UV Spectrophotometer (UV Prove v2.1) at 260 nm.…”

CYP2C19*2, CYP2C19*17 and ITGB3 (PlA1/A2) polymorphisms and resulting therapeutic alterations of clopidogrel and aspirin: A clinical screening among CVD patients who undergone PCI

“…Substantial clinical trials that evaluated higher loading and maintenance dose of clopidogrel in ACS/PCI patients have resolved that adjusting the dose does not downgrade the incidence of death [35]. Prasugrel and ticagrelor, on the other hand, were superior to clopidogrel in a large-scale randomized trial of ACS patients with planned PCI which showed 42% and 26 % reduction in-stent thrombosis, respectively [36].…”

“…However, these may not replace clopidogrel for all kinds of patients due to contraindication in some patients [36], insufficient long-term toxicity data [37] and also lack of statistically significant data [38].…”