April 4, 2007: Mark W. Linder, PhD, DABCC
Warfarin is one of the most widely prescribed oral anticoagulants. However, optimal use of the drug has been hampered by its >10-fold interpatient variability in the doses required to attain therapeutic responses. Warfarin acts by interfering with the recycling of vitamin K in the liver, which leads to reduced activation of several clotting factors. As many as thirty genes may be involved in the biotransformation and mode of action of warfarin, with CYP2C9 and VKORC1 being the most important genes affecting the pharmacokinetic and pharmacodynamic parameters of warfarin. These two genes, together with environmental factors, partly explain the interindividual variation in warfarin dose requirements. Large ongoing studies of genes involved in the actions of warfarin, together with prospective assessment of environmental factors, will undoubtedly increase the capacity to accurately predict warfarin dose. Implementation of pre-prescription genotyping and individualized warfarin therapy represents an opportunity to minimize the risk of hemorrhage without compromising effectiveness.