Back to Search
Start Over
The Pharmacogenetics and Pharmacodynamics of Clopidogrel Response
- Source :
- JACC: Cardiovascular Interventions. 1(6):620-627
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- Objectives This study assessed the effect of pharmacogenetics on the antiplatelet effect of clopidogrel. Background Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 [CYP] family), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate–receptor P2Y12). Methods Sixty patients undergoing elective percutaneous coronary intervention in the randomized PRINC (Plavix Response in Coronary Intervention) trial had platelet function measured using the VerifyNow P2Y12 analyzer after a 600-mg or split 1,200-mg loading dose and after a 75- or 150-mg daily maintenance dosage. Polymerase chain reaction–based genotyping evaluated polymorphisms in the CYP2C19, CYP2C9, CYP3A4, CYP3A5, ABCB1, P2Y12, and CES genes. Results CYP2C19*1*1 carriers had greater platelet inhibition 2 h after a 600-mg dose (median: 23%, range: 0% to 66%), compared with platelet inhibition in CYP2C19*2 or *4 carriers (10%, 0% to 56%, p = 0.029) and CYP2C19*17 carriers (9%, 0% to 98%, p = 0.026). CYP2C19*2 or *4 carriers had greater platelet inhibition with the higher loading dose than with the lower dose at 4 h (37%, 8% to 87% vs. 14%, 0% to 22%, p = 0.002) and responded better with the higher maintenance dose regimen (51%, 15% to 86% vs. 14%, 0% to 67%, p = 0.042). Conclusions Carriers of the CYP2C19*2 and *4 alleles showed reduced platelet inhibition after a clopidogrel 600-mg loading dose but responded to higher loading and maintenance dose regimens. Genotyping for the relevant gene polymorphisms may help to individualize and optimize clopidogrel treatment. (Australia New Zealand Clinical Trials Registry; ACTRN12606000129583)
- Subjects :
- medicine.medical_specialty
Maintenance dose
business.industry
medicine.medical_treatment
Percutaneous coronary intervention
CYP2C19
Clopidogrel
Gastroenterology
Loading dose
P2Y12
Anesthesia
Pharmacodynamics
Internal medicine
medicine
business
Cardiology and Cardiovascular Medicine
Pharmacogenetics
medicine.drug
Subjects
Details
- ISSN :
- 19368798
- Volume :
- 1
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- JACC: Cardiovascular Interventions
- Accession number :
- edsair.doi.dedup.....6705f397860309c88886fb81c3960986
- Full Text :
- https://doi.org/10.1016/j.jcin.2008.09.008