THE EFFECT OF ANTICONVULSANT DRUGS WHICH INDUCE LIVER MICROSOMAL ENZYMES ON DERIVED AND INGESTED PHENOBARBITONE LEVELS

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Abstract
A comparison was made between the levels of derived phenobarbitone in 3 groups of patients who were taking Primidone as a single drug, Primidone with phenytoin and Primidone in combination with phenytoin and carbamazepine. The levels of ingested phenobarbitone when this drug alone was taken were compared with the levels when phenobarbitone was taken in combination with phenytoin in 2 other groups of patients. A significant increase in derived phenobarbitone levels occurred when Primidone was used in combination with phenytoin alone or with phenytoin and carbamazepine. The highest level occurred in a group of patients taking the 3 drug combination. There was no significant difference between the levels of ingested phenobarbitone when this drug was used as single therapy or in combination with phenytoin. The increase in derived phenobarbitone levels appears to relate to the effect of phenytoin on liver enzyme systems. The greater increase with triple therapy may be related to the combined effect of carbamazepine and phenytoin on microsomal enzymes. As there was no increase in ingested phenobarbitone levels when this drug was taken in combination with phenytoin, previous suggestions were unable to be confirmed that phenytoin either inhibits the hydroxylation of phenobarbitone or impairs its renal excretion.