After oral absorption, warfarin is transported to the liver where CYP1A1, CYP1A2, and CYP3A4 metabolize the R-enantiomer and CYP2C9 metabolizes the more potent S-enantiomer. Warfarin inhibits vitamin K reductase, which is synthesized (at least in part) byVKORC1. By impairing the regeneration of the reduced form of vitamin K, R- and S-warfarin interfere with the vitamin-K–dependent carboxylation of clotting factors prothrombin (II), VII, IX, and X.

Reprinted with permission from Gage BF, van Walraven C, Pearce L, et al. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation. 2004;110:2287–2292.