Key result
The ABCB1 3435C>T polymorphism (TT genotype) was associated with significantly lower clopidogrel exposure compared to CC and CT genotypes (P=0.012), but did not affect platelet aggregation.
Why the study?
Does the ABCB1 3435C>T polymorphism influence the pharmacokinetics and pharmacodynamics of clopidogrel in patients undergoing elective coronary angiography and PCI?
Observational (n=42)
Does the ABCB1 3435C>T polymorphism influence the pharmacokinetics and pharmacodynamics of clopidogrel in patients undergoing elective coronary angiography and PCI?
The ABCB1 3435C>T polymorphism affects the pharmacokinetics of unchanged clopidogrel but does not significantly alter its antiplatelet efficacy.
Answers are grounded in this paper and cite their sources.
ABCB1 3435C>T TT genotype does not alter clopidogrel antiplatelet efficacy; leaves open whether genotyping improves PCI outcomes.
WHAT IS KNOWN AND OBJECTIVE: The reasons of clopidogrel (CLP) resistance are still unclear. The response to CLP may be influenced by both genetic and non-genetic factors. Among genetic factors, common polymorphisms in the gene coding glycoprotein-P (P-gp, MDR1 and ABCB1) are considered as potential determinants of the efficacy of CLP treatment. The aim of this study was to evaluate the influence of ABCB1 3435C>T genetic polymorphism on the pharmacokinetics and pharmacodynamics of CLP and its metabolites: diastereoisomers of thiol metabolite (the inactive H3 and the active H4) and inactive carboxylic derivative. METHODS: The study group included 42 patients undergoing elective coronary angiography and percutaneous coronary intervention. The plasma concentrations of CLP and its metabolites were measured by a validated HPLC-MS/MS method. Whole-blood aggregation was determined with Multiplate analyzer. For evaluation of ABCB1 3435C>T polymorphism, PCR-RFLP method was applied. RESULTS AND DISCUSSION: It was found that Exposition to the unchanged CLP, measured by AUC0-t of the drug, was significantly lower (P = 0·012) in TT homozygotes comparing to that observed in CC and CT genotypes, although no correlation was found between platelet aggregation and ABCB1 genetic polymorphism. WHAT IS NEW AND CONCLUSION: Our findings show that the presence of 3435C>T allele has an impact on CLP pharmacokinetics but not on the drug pharmacodynamics. Therefore, the 3435C>T genotype may not be the primary determinant influencing the pharmacokinetics of the active H4 metabolite and antiplatelet effect of the drug.
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Karaźniewicz‐Łada et al. (2014) conducted an observational in elective coronary angiography and percutaneous coronary intervention (n=42). ABCB1 3435C>T genetic polymorphism (TT genotype) vs. CC and CT genotypes was evaluated on Exposition to the unchanged clopidogrel, measured by AUC0-t (p=0.012). The ABCB1 3435C>T polymorphism (TT genotype) was associated with significantly lower clopidogrel exposure compared to CC and CT genotypes (P=0.012), but did not affect platelet aggregation.
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