Increased Bishydroxycoumarin Requirements in Patients Receiving Phenobarbital

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Abstract
SEVERAL drugs1 2 3 4 5 have recently been shown to increase the activity of drug-metabolizing enzymes in the liver microsomes. Phenobarbital is particularly able to stimulate an increase in the synthesis of a variety of drug-metabolizing enzymes. The activity of liver microsomal enzymes that metabolize diphenylhydantoin,6 griseofulvin,7 zoxazolamine,8 strychnine9 and coumarins10 has been shown to be increased by phenobarbital.The effect of barbiturates on the activity of coumarins has been reported in animals, and in single-dose acute experiments in man.10 A single patient, receiving bishydroxycoumarin (Dicumarol) over a prolonged period, has been reported to have had a substantial decrease in plasma anticoagulant level . . .