Why the study?
Do genetic co-factors such as the CYP2C19*2 allele influence the pharmacokinetics and active metabolite exposure of clopidogrel?
Do genetic co-factors such as the CYP2C19*2 allele influence the pharmacokinetics and active metabolite exposure of clopidogrel?
The CYP2C19*2 allele is the only significant covariate that lowers the conversion of clopidogrel to its active metabolite, thereby reducing systemic exposure.
Answers are grounded in this paper and cite their sources.
CYP2C19*2 carriage was associated with lower clopidogrel active metabolite exposure; leaves open whether genotyping should guide therapy.
PURPOSE: A high interindividual variability is observed in the pharmacokinetics of clopidogrel, a widely used antiplatelet drug. In the present study, a joint parent-metabolite population pharmacokinetic model was developed to adequately describe observed concentrations of clopidogrel and its active thiol metabolite (H4). RESULTS: It was found that the only significant covariate was the presence of CYP2C19*2 allele, which had an impact on lower conversion of clopidogrel to H4. As a result, predicted area under the time-concentration curve values was lower in carriers of this allele, with median 5.94 ng h/ml (interquartile range 3.92-12.51 [ng∙h/ml]) vs. 12.70 ng h/ml in non-carriers (interquartile range, 7.00-19.39 [ng∙h/ml]), respectively (p = 0.004). CONCLUSIONS: Developed model predicts that the only significant covariate influencing the observed concentrations and therefore the exposure to the active H4 metabolite is the presence of CYP2C19*2 allele.
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Danielak et al. (2017) studied this question.
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