119 - Pharmacogenetics of oral anticoagulant therapy
Autor(s): G. Lippi
Issue: RIMeL - IJLaM, Vol. 5, N. 3-S1, 2009 (MAF Servizi srl ed.)
Page(s): 119
Oral anticoagulant therapy (OAT) based on coumarins (warfarin, Coumadin) and other vitamin K antagonists (acenocoumarol, Syntrom) has been the cornerstone of prevention and treatment of several thrombotic disorders, and these compounds are still the most used anticoagulant medications worldwide. Warfarin is a racemic mixture of two optically active enantiomers; S-warfarin is prevalently metabolized by the CYP2C9 enzyme of the cytochrome P450 system, whereas R-warfarin is cleared by the two cytochrome enzymes 1A2 and 3A4 (CYP1A2 and CYP3A4). Warfarin and other coumarins produce their anticoagulant effect by contrasting the cyclic inter-conversion of vitamin K to its 2,3 epoxide. The enzymes vitamin K epoxide reductase (VKOR) and vitamin K reductase are essential in this process, because they reduce the vitamin K 2,3-epoxide to the active vitamin K quinole cofactor.……