Abstract
Genotyping has the potential to improve the efficacy and safety of major antithrombotic drugs. For warfarin, the stable maintenance dose varies from 1-10 mg/day. The VKORC1 -1639G>A allele and the CYP2C9*2 and *3 alleles (cumulative frequency: 90% in Asians, 65% in Europeans and 20% in Africans), explain 45% of response variability in European and 30% in African populations. The large clinical trials COAG and EU-PACT will define the extent to which pharmacogenetic dosing affects the safety and efficacy of warfarin and coumarin derivatives. The platelet inhibitor clopidogrel requires activation by the CYP2C19 enzyme. CYP2C19*2 and *3 alleles (cumulative frequency: 20-50%) produce null enzyme activity, and their presence attenuates platelet inhibition and increases cardiovascular events. The US FDA-mandated drug labeling recognizes the relevance of genotyping in the selection and dosing of both warfarin and clopidogrel.
Publication types
-
Research Support, N.I.H., Extramural
-
Review
MeSH terms
-
Anticoagulants / pharmacology
-
Anticoagulants / therapeutic use*
-
Aryl Hydrocarbon Hydroxylases / genetics
-
Clopidogrel
-
Cost-Benefit Analysis
-
Cytochrome P-450 CYP2C19
-
Cytochrome P-450 CYP2C9
-
Cytochrome P-450 Enzyme System / genetics
-
Cytochrome P450 Family 4
-
Dose-Response Relationship, Drug
-
Genetic Privacy
-
Genotype
-
Health Policy
-
Humans
-
Mixed Function Oxygenases / genetics
-
Pharmacogenetics*
-
Piperazines / pharmacology
-
Piperazines / therapeutic use
-
Platelet Aggregation Inhibitors / pharmacology
-
Platelet Aggregation Inhibitors / therapeutic use*
-
Polymorphism, Single Nucleotide
-
Prasugrel Hydrochloride
-
Precision Medicine
-
Purinergic P2 Receptor Antagonists
-
Thiophenes / pharmacology
-
Thiophenes / therapeutic use
-
Ticlopidine / analogs & derivatives
-
Ticlopidine / pharmacology
-
Ticlopidine / therapeutic use
-
Vitamin K Epoxide Reductases
-
Warfarin / pharmacology
-
Warfarin / therapeutic use
Substances
-
Anticoagulants
-
Piperazines
-
Platelet Aggregation Inhibitors
-
Purinergic P2 Receptor Antagonists
-
Thiophenes
-
Warfarin
-
Cytochrome P-450 Enzyme System
-
Clopidogrel
-
Mixed Function Oxygenases
-
CYP2C9 protein, human
-
Cytochrome P-450 CYP2C9
-
Aryl Hydrocarbon Hydroxylases
-
CYP2C19 protein, human
-
Cytochrome P-450 CYP2C19
-
Cytochrome P450 Family 4
-
CYP4F2 protein, human
-
VKORC1 protein, human
-
Vitamin K Epoxide Reductases
-
Prasugrel Hydrochloride
-
Ticlopidine