Pharmacogenetics of coumarinic oral anticoagulants.
Coumarinic oral anticoagulants are life-saving drugs, but are also one of the leading causes of drug-induced major bleeding events. Moreover, there is substantial individual variation in response to coumarinic oral anticoagulants caused by several factors including variations in the CYP2C9 and VKORC1 genes. Several retrospective and a few small prospective clinical studies have shown that polymorphisms in CYP2C9 and VKORC1 genes together account for 35-50% of the variability in warfarin initiation and maintenance dose requirements. Large randomized clinical trials are currently underway to further solidify the safety, clinical utility and cost-effectiveness of pharmacogenetic-guided dosing algorithms for warfarin, acenocoumarol and phenprocoumon. By 2020, coumarinic oral anticoagulant pharmacogenetic testing will be part of routine clinical practice in anticoagulant therapy.
Manolopoulos
Vangelis G
VG
Laboratory of Pharmacology & Clinical Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece. emanolop@med.duth.gr
Ragia
Georgia
G
Tavridou
Anna
A
D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D003374:Coumarins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D010597:Pharmacogenetics / Q000379:methods* / Q000639:trends; D016032:Randomized Controlled Trials as Topic; D064417:Vitamin K Epoxide Reductases
D000925:Anticoagulants; D003374:Coumarins; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases