Clopidogrel Pharmacokinetics and Pharmacodynamics Vary Widely Despite Exclusion or Control of Polymorphisms (CYP2C19, ABCB1, PON1), Noncompliance, Diet, Smoking, Co-Medications (Including Proton Pump Inhibitors), and Pre-Existent Variability in Platelet Function

• Published in: Journal of the American College of Cardiology Vol. 61; no. 8; pp. 872 - 879
• Main Authors: Frelinger, Andrew L., Bhatt, Deepak L., Lee, Ronald D., Mulford, Darcy J., Wu, Jingtao, Nudurupati, Sai, Nigam, Anu, Lampa, Michael, Brooks, Julie K., Barnard, Marc R., Michelson, Alan D.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 26.02.2013; Elsevier; Elsevier Limited
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles - administration & dosage; 2-Pyridinylmethylsulfinylbenzimidazoles - pharmacokinetics; Acute coronary syndromes; Adult; Area Under Curve; Aryl Hydrocarbon Hydroxylases - genetics; Aryldialkylphosphatase - genetics; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Biological and medical sciences; Blood Coagulation - drug effects; Body mass index; Cardiology; Cardiology. Vascular system; Cardiovascular; Cardiovascular Diseases - blood; Cardiovascular Diseases - etiology; Cardiovascular Diseases - prevention & control; Cardiovascular Diseases - psychology; Confounding Factors (Epidemiology); Cross-Over Studies; Cytochrome; Cytochrome P-450 CYP2C19; Demographics; Drug dosages; Drug Interactions; Drug Monitoring - methods; Drug therapy; Drug Therapy, Combination; drugs; Female; Genotype & phenotype; Humans; Male; Medical sciences; Middle Aged; Nutrition research; Patient Compliance; pharmacokinetics; Platelet Aggregation - drug effects; Platelet Aggregation - genetics; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - pharmacokinetics; Platelet Function Tests - methods; platelets; Polymorphism, Genetic; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - pharmacokinetics; receptors; risk factors; Smoking - metabolism; Studies; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacokinetics; Tobacco, tobacco smoking; Toxicology; United States > US; California; VASP; Cmax; CVs; risk factors; receptors; Rx drugs; drugs; OTC drugs; PRI; PON1; PPI; ADP; platelets; PRP; PRU; ClopidogrelAM; Pre-Tx; pharmacokinetics; LTA; AUCt; BMI; EM/EM; MPA; over-the-counter drugs; paraoxonase 1; P2Y 12 reaction units; pre-treatment; C max; proton pump inhibitor; vasodilator stimulated phosphoprotein; platelet reactivity index; prescription drugs; AUC t; adenosine phosphate; clopidogrel active metabolite; coefficients of variation; peak plasma concentration; body mass index; light transmission aggregation; platelet rich plasma; area under the time-concentration curve; maximal platelet aggregation; homozygous CYP2C19 extensive metabolizer genotype; Clopidogrel AM; Compliance; Variability; Tobacco smoking; Check; Biological activity; Antiplatelet agent; Proton pump inhibitor; Prevention; Chemotherapy; Control; Treatment; Diet; Platelet function; Clopidogrel; Circulatory system; Cardiology; Pharmacokinetics; Polymorphism

This study sought to determine whether known genetic, drug, dietary, compliance, and lifestyle factors affecting clopidogrel absorption and metabolism fully account for the variability in clopidogrel pharmacokinetics and pharmacodynamics. Platelet inhibition by clopidogrel is highly variable. Patien...