Format

Send to

Choose Destination

See 1 citation found by title matching your search:

J Clin Pharm Ther. 2015 Apr;40(2):226-31. doi: 10.1111/jcpt.12236. Epub 2014 Nov 28.

Impact of common ABCB1 polymorphism on pharmacokinetics and pharmacodynamics of clopidogrel and its metabolites.

Author information

1
Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznań, Poland.

Abstract

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.

KEYWORDS:

P-glycoprotein; clopidogrel; pharmacogenetics; pharmacokinetics; platelet aggregation

PMID:
25430046
DOI:
10.1111/jcpt.12236
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center