Pharmacokinetics:
Absorption: Readily absorbed from the GI tract; can also be absorbed through the skin. Time to peak plasma concentration: Approx 4 hr (oral).
Distribution: Crosses the placenta. Volume of distribution: 0.14 L/kg. Plasma protein binding: 99% (mainly albumin).
Metabolism: Racemic warfarin is stereoselectively metabolised by hepatic CYP450 microsomal enzymes (CYP2C9, CYP2C19, CYP2C8, CYP2C18, CYP1A2 and CYP3A4) to inactive metabolites. R-warfarin by CYP1A2 and CYP3A4 isoenzymes to diastereoisomeric alcohols; S-warfarin principally via oxidation by CYP2C9 isoenzyme to 7-hydroxywarfarin.
Excretion: Via urine (92%, primarily as metabolites). Plasma half-life: Approx 40 hr.