WARFARIN AND OTHER ORAL ANTICOAGULANTS

Warfarin, phenprocoumon and acenocoumarol are racemic mixtures of S- and R- enantiomers. The S-enantiomers of these coumarins have several times more anticoagulant activity than the R-enantiomers. The S-enantiomer of warfarin is metabolised primarily by CYP2C9. The metabolism of R-warfarin is more complex but this enantiomer is primarily metabolised by CYP1A2, CYP3A4, and CYP2C19. There is much more known about the metabolism of warfarin compared to other antico- agulants but it is established that S-phenprocoumon and S-acenocoumarol are also substrates for CYP2C9. Whilst the metabolism of the coumarins, especially warfarin, is well known, the numerous interaction pathways and the variability in patient responses makes the clinical consequences of alterations in metabolism difficult to predict.
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