Phenobarbital Dicoumarol

Dicoumarol Phenobarbital Phenytoin Risk of toxicity, particularly with phenytoin Inhibition of metabolism of the object drugs... 

CI2. Cucinell, S. A., Conney, A. H., Sansor, M., and Bums, J. J., Drug interactions in man lowering effect of phenobarbital on plasma levels of dicoumarol and diphenylhydantoin. Clin. Pharmacol. Thcr. 6, 420-429 (1965). 

In addition to enzyme induction, phenobarbital can reduce dicoumarol absorption. 

Dicoumarol, warfarin and tromexan (67) have been shown to be metabolised by hepatic microsomal enzymes. These enzymes can be increased by phenobarbital and with the rapid metabolism of the anticoagulant its effect is reduced [451]. In contrast, phenyramidol inhibits the metabolism of coumarin and hence prolongs the duration of the anticoagulant response [445]. In the rat, the major metabolites of these compounds are 7-hydroxylated derivatives (68) [460— 462]. In man, besides the alteration of the ring [463], side-chain hydroxylation also occurs (69) in the rabbit, de-esterification proceeds rapidly (70) (see Figure 3.9). 

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