Determination of the plasma half life of antipyrine has been used by many workers as a measure of an individual's drug metabolizing ability, and there is some evidence to suggest that this procedure provides a particularly sensitive index of induction. In the present work, carried out in 7 epileptic patients on various anticonvulsants, the mean plasma half life value of antipyrine (±SD) was 4.8 ± 0.5 h. This was significantly shorter than the mean values of 12.1 h in controls and 7.8 h in subjects receiving hypnotic doses of amylobarbitone, but was similar to the figures of 5.3 h reported for barbiturate dependent patients and 4.8 h in barbiturate overdose patients. Judging by this simple index, patients on anticonvulsant drugs have a markedly increased durg metabolizing ability and are probably particularly at risk with regard to drug interactions or problems associated with the increased breakdown of endogenous substances. In a rat study, the effects of 4 days treatment with 10 mg/kg and 100 mg/kg of each of 15 different anticonvulsant drugs were compared. Liver cytochrome P-450 levels and in vitro oxidation of hexobarbitone were used as indices. Marked induction (i.e. more than 5 fold increase in hexobarbitone oxidation after treatment with 100 mg/kg) occurred with ethosuximide, methoin, methylphenobarbitone, phenobarbitone, phenylmethylbarbituric acid and primidone, the last two drugs producing the greatest induction response. A lesser induction (more than 3 fold increase) was found with carbamazepine, phenytoin, ethotoin, methsuximide and pheneturide, while beclamide, paradione and troxidone had little or no effect. Of the 15 anticonvulsant drugs studied, the only one for which there was any suggestion of an inhibitory effect on drug metabolism when administered in this way was sulthiame.
|Original language||English (US)|
|Number of pages||10|
|State||Published - 1976|
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