(R)-Acenocoumarol

Acenocoumarol is a short-lived oral anti-coagulant, which, like warfarin, functions by inhibiting vitamin K epoxide reductase. It has higher intrinsic anticoagulant potency than warfarin and phenprocoumon, when evaluated in vitro. Acenocoumarol has a single chiral center that gives rise to two different enantiomeric forms. (R)-Acenocoumarol has a longer plasma elimination half-life (6.6 hours) and slower plasma clearance (1.9 L/hour), compared to the (S)-enantiomer (1.8 hours, 28.5 L/hour). The R-enantiomer is rapidly absorbed from the gastrointestinal tract with essentially complete oral bioavailability, whereas (S)-acenocoumarol undergoes extensive first-pass metabolism. Perhaps related to these pharmacokinetic characteristics, (R)-acenocoumarol is more potent in vivo as an anti-coagulant than the (S)-enantiomer. As the clearance of acenocoumarol is ~20-fold faster than that for warfarin, the plasma concentrations of acenocoumarol are substantially lower than those for warfarin in patients receiving long-term treatment.