The elimination of Warfarin is almost entirely by metabolism. Warfarin is stereoselectively metabolized by hepatic cytochrome P-450 (CYP450) microsomal enzymes to inactive hydroxylated metabolites (predominant route) and by reductases to reduced metabolites (Warfarin alcohols) with minimal anticoagulant activity. Identified metabolites of Warfarin include dehydroWarfarin, two diastereoisomer alcohols, and 4′-, 6-, 7-, 8-, and 10-hydroxyWarfarin. The CYP450 isozymes involved in the metabolism of Warfarin include CYP2C9, 2C19, 2C8, 2C18, 1A2, and 3A4. CYP2C9, a polymorphic enzyme, is likely to be the principal form of human liver CYP450 that modulates the in vivo anticoagulant activity of Warfarin. Patients with one or more variant CYP2C9 alleles have decreased S-Warfarin clearance [see Clinical Pharmacology ( )].