Warfarin and vitamin K intake in the era of pharmacogenetics.
The considerable variability in the warfarin dose-response relationship between individuals, is explained mainly by genetic variation in its major metabolic (CYP2C9) and target (VKORC1) enzymes. Despite the predominance of pharmacogenetics, environmental factors also affect the pharmacokinetics and pharmacodynamics of warfarin, and are often overlooked. Among these factors, dietary and supplemental vitamin K consumption is a controllable contributor to within-, and between-patient variability of warfarin sensitivity. In this commentary we review the current role of vitamin K in warfarin anticoagulation therapy, with emphasis on the following: 1 The effect of dietary and supplemental vitamin K on warfarin anticoagulation, beyond the impact of genetic variability in CYP2C9 and VKORC1. We deal separately with the effects of vitamin K on warfarin dose requirements during the induction of therapy, as opposed to its effect on stability of anticoagulation control during maintenance therapy. 2 The role of vitamin K supplementation in warfarin treated patients with vitamin K deficiency as well as in patients with unstable warfarin anticoagulation, and 3 The role of therapeutic vitamin K in cases of warfarin over-anticoagulation.
Lurie
Yael
Y
Institute of Clinical Pharmacology and Toxicology, Chaim Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Loebstein
Ronen
R
Kurnik
Daniel
D
Almog
Shlomo
S
Halkin
Hillel
H
D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001777:Blood Coagulation / Q000187:drug effects* / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D009154:Mutation; D014812:Vitamin K / Q000008:administration & dosage* / Q000494:pharmacology; D014813:Vitamin K Deficiency / Q000188:drug therapy; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases