Orfarin

Orfarin Mechanism of Action

warfarin

Manufacturer:

Orion Pharma

Distributor:

Apex
Full Prescribing Info
Action
Pharmacotherapeutic group: Oral anticoagulants. ATC­ code: B01AA03.
Pharmacology: Pharmacodynamics: Warfarin or 4­-hydroxycoumarin is an anticoagulant that prevents the vitamin K dependent synthesis of clotting factors. Of its isomers, S-warfarin is approximately 5 times as potent an anticoagulant as R-­warfarin. The effect of warfarin is based on its ability to prevent the reduction and activity of vitamin K in the synthesis of coagulation factors II, VII, IX, and X. In therapeutic doses, warfarin prevents the synthesis of vitamin K-­dependent coagulation factors by 30 to 50% and reduces the biological activity of coagulation factors. It takes 2 to 7 days for the full effect of warfarin to appear. During this time the coagulation factors already synthesised are eliminated.
Pharmacokinetics: The bioavailability of oral warfarin is over 90% and peak plasma concentration is achieved in 3 to 9 hours. Meals slow down but do not reduce the absorption. Enterohepatic circulation does exist. Warfarin binds strongly to serum albumin, the free fraction varies between 0.5 and 3%. The volume of distribution of warfarin is approximately 0.14 l/kg. Warfarin crosses the placenta but is not excreted in the breast milk. Warfarin is metabolised in the liver catalysed by CYP2C9 (S-warfarin) and CYP1A2 and CYP3A (R-warfarin) into inactive metabolites which are excreted in the urine. The elimination half-life of S-­warfarin is 18 to 35 hours and that of R-­warfarin 20 to 70 hours.
Toxicology: Preclinical safety data: LD50 in mice is approximately 1500 mg/kg orally, 750 mg/kg intraperitoneally, and in rats approximately 10­-100 mg/kg orally. The toxicity manifested as different bleeding complications. Chronic toxicity has not been studied in animals. Warfarin is a teratogenic compound and when used in experimental animals throughout the gestation, it increased the fetal and neonatal mortality. Changes in growth plates and maxillonasal hypoplasia were observed in rats. The genotoxicity and carcinogenicity have not been investigated.
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