Warfarin
Warfarin. Inhibits vitamin K epoxide reductase (VKOR) → depletes reduced vitamin K → prevents γ-carboxylation of factors II, VII, IX, X +… Oral half-life 40 h.
Inhibits vitamin K epoxide reductase (VKOR) → depletes reduced vitamin K → prevents γ-carboxylation of factors II, VII, IX, X + proteins C/S. Narrow therapeutic index + massive interaction list + dietary K variability → DOACs (apixaban, rivaroxaban) now preferred for non-valvular indications.
PK: RE-POINTED WITHOUT OVERWRITING, AND THE REASON MATTERS. Its previous citation was a nebicapone interaction study reporting R- and S-warfarin peak and exposure values and no absorption rate, volume, bioavailability or half-life — class 1 for all four. The obvious replacement is already in this record refs[] and is fully self-consistent to three digits: "It distributes into a small volume of distribution (10 L/70kg) and is eliminated by hepatic metabolism with a very small clearance (0.2 L/h/70kg). The elimination half-life is about 35 hours." BUT ADOPTING IT WOULD MAKE THE MODEL WORSE: that set predicts an exposure BELOW the previously cited study own truncated observation, where the stored values bracket it. The stored numbers are label-grade and empirically defensible, so the citation moves and the values do not. THE STORED HALF-LIFE REPRESENTS NEITHER ENANTIOMER. Warfarin is a racemate whose two halves are kinetically different drugs: S-warfarin, which carries three to five times the anticoagulant potency, has a verbatim half-life of 25 h, while R-warfarin runs 37 to 47.8 h. 40 h is the label racemic figure, so THE MODEL OVER-PERSISTS THE ENANTIOMER DOING MOST OF THE WORK BY ABOUT 1.6x, and the schema cannot express two clearances. MY CROSS-ENANTIOMER-MEAN HYPOTHESIS WAS REFUTED — 40 is not the mean of any published pair — but the substance of the concern is worse than a mean would have been. ITS EMPTY effect_compartment IS CORRECT: warfarin PD is clotting-factor turnover, "the elimination half-life estimated from changes in prothrombin time is approximately 17 hours", so a keo here would have to be about 0.04/h, TWENTY-FIVE TIMES SMALLER than the 0.5-1/h its four sibling records carry. It must not inherit that default.
Pharmacokinetics
- Oral — t½ 40 h · F 95% · Vd 8 L
Related compounds
- Vitamin K1 — major
- Vitamin K2 MK-7 — major
- Vitamin E — caution
- St. John's Wort — major
- Cholestyramine — caution
- Acetaminophen — caution
- Apixaban — caution
- Dabigatran — caution
Sources: PMID:3542339, PMID:15911722, PMID:18679669, PMID:6661352, PMID:2938614