Warfarin and other coumarin derivatives: pharmacokinetics, pharmacodynamics, and drug interactions

Abstract

Warfarin, a racemic mixture of R- and S-enantiomers, exerts its anticoagulant effect by interfering with the hepatic synthesis of vitamin K-dependent clotting factors II, VII, IX, and X and proteins C and S. Warfarin displays stereospecific pharmacokinetic and pharmacodynamic properties, and the isomers are differentially metabolized by cytochrome p450 isozymes. Among patients treated with warfarin, there is little correlation among dose, serum concentration, and therapeutic effect, necessitating individualized dosing guided by therapeutic monitoring of the prothrombin time. The pharmacokinetic and pharmacodynamic properties of warfarin as well as its narrow therapeutic index make it particularly susceptible to interactions with other prescription and nonprescription drugs, including dietary supplements. Numerous drug compounds are reported to interact with warfarin, necessitating increased prothrombin time monitoring and warfarin dosing adjustments to maintain safe and effective anticoagulation.