The Pharmacogenetics and Pharmacodynamics of Clopidogrel Response

• Published in: JACC. Cardiovascular interventions 2008-12, Vol.1 (6), p.620-627
• Main Authors: Gladding, Patrick, FRACP, Webster, Mark, FRACP, Zeng, Irene, MSc, Farrell, Helen, BHSc, Stewart, Jim, FRACP, Ruygrok, Peter, FRACP, Ormiston, John, FRACP, El-Jack, Seif, FRACP, Armstrong, Guy, FRACP, Kay, Patrick, FRACP, Scott, Douglas, FRACP, Gunes, Arzu, MD, PhD, Dahl, Marja-Liisa, MD, PhD
• Format: Article
• Language: English
• Subjects: antiplatelets; Cardiovascular; clopidogrel; pharmacogenetics
• ISSN: 1936-8798; 1876-7605
• DOI: 10.1016/j.jcin.2008.09.008

The Pharmacogenetics and Pharmacodynamics of Clopidogrel Response: An Analysis From the PRINC (Plavix Response in Coronary Intervention) Trial Patrick Gladding, Mark Webster, Irene Zeng, Helen Farrell, Jim Stewart, Peter Ruygrok, John Ormiston, Seif El-Jack, Guy Armstrong, Patrick Kay, Douglas Scott, Arzu Gunes, Marja Liisa-Dahl Pharmacogenomics might explain the variability in clopidogrel response. Sixty patients undergoing elective percutaneous coronary intervention were genotyped for polymorphisms in CYP2C19 , CYP2C9 , CYP3A4, CYP3A5 , ABCB1, P2Y12 , and CES genes. C YP2C1911 carriers had greater platelet inhibition 2 h after a 600-mg dose than CYP2C192, 4 , or 17 carriers did. CYP2C192 or 4 carriers had greater platelet inhibition with a split 1,200-mg dose than with a 600-mg loading dose, and with a 150-mg compared with a 75-mg daily maintenance dosage. Those with CYP2C192 and 4 showed reduced platelet inhibition after clopidogrel 600 mg, but responded to higher loading and maintenance dose regimens