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Omeprazole, pantoprazole, and CYP2C19 effects on clopidogrel pharmacokinetic-pharmacodynamic relationships in stable coronary artery disease patients.
- Source :
-
European Journal of Clinical Pharmacology . Sep2015, Vol. 71 Issue 9, p1059-1066. 8p. 3 Charts, 3 Graphs. - Publication Year :
- 2015
-
Abstract
- Purpose: Proton-pump Inhibitors use and CYP2C19 loss-of-function alleles are associated with reduced responsiveness to standard clopidogrel doses and increased cardiovascular events. Methods: Post-myocardial infarction patients heterozygous (wild type [wt]/*2, n = 41) or homozygous (*2/*2, n = 7) for the CYP2C19* 2 genetic variant were matched with patients not carrying the variant (wt/wt, n = 58). All patients were randomized to a 300- or 900-mg clopidogrel loading dose. A PK/PD model was defined using the variation of the P2Y reaction unit relative to baseline. Results: Carriage of CYP2C19* 2 allele and the use of omeprazole/esomeprazole were associated with the inter-individual variability in the active metabolite clearance. The relationship between inhibition of platelet aggregation (IPA, %) and the active metabolite AUC (h*μg/L) was described by a sigmoid function (Emax 56±5%; E 15.9±0.8 h*μg/L) with a gamma exponent (7.04±2.26). Conclusion: This on/off shape explains that a small variation of exposure may have a clinical relevance. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ALLELES
*BIOTRANSFORMATION (Metabolism)
*BLOOD platelet aggregation
*CHI-squared test
*CONFIDENCE intervals
*DRUG interactions
*DOSE-effect relationship in pharmacology
*GENETIC polymorphisms
*MYOCARDIAL infarction
*OMEPRAZOLE
*OXIDOREDUCTASES
*PROBABILITY theory
*T-test (Statistics)
*PROTON pump inhibitors
*BODY mass index
*CLOPIDOGREL
*DATA analysis software
*PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00316970
- Volume :
- 71
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- European Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 108841019
- Full Text :
- https://doi.org/10.1007/s00228-015-1882-3