Studies on Coumarin Anticoagulant Drugs

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Abstract
Thirty normal subjects were given a single loading dose of warfarin sodium, 1.5 mg/kg of body weight. The drug was metabolized slowly (mean biological half-life, 47 hr) and showed a prolonged biological effect (over 6 days). In two separate experiments no loading dose was given; instead, daily doses of 15 mg and 10 mg were administered to 15 of the subjects. The prothrombin complex responses were compared with those obtained in the same subjects after the large loading dose. The mean time in days to reach the therapeutic range (prothrombin complex activity<35% of normal) was 1.1 days with the dose of 1.5 mg/kg of body weight, 2.7 days with the dose of 15 mg/day, and 5.2 days with 10 mg/day. With all three methods the therapeutic range was reached soon after a level of warfarin of 2 mg/L plasma was attained.