Genetic control of the phenobarbital-induced shortening of plasma antipyrine half-lives in man

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Abstract

The mean half-life of antipyrine in the plasma of four sets of identical and four sets of fraternal twins after a single oral dose of 16 mg/kg of antipyrine was 12.7 ±SD 3.3 hr. After 2 wk on sodium phenobarbital (2 mg/kg daily) the half-life of antipyrine in the plasma of these twins was reduced to 8.0 ±SD 1.5 hr. Shortening of the plasma antipyrine half-life occurred in all but one of these 16 normal, adult volunteers, but there was considerable variation in the extent of reduction which ranged from 0 to 69%. Phenobarbital administration decreased individual variations in antipyrine metabolism as indicated by the smaller standard deviation of the plasma antipyrine half-lives after phenobarbital than observed initially and by the narrowed range of variation in plasma antipyrine half-lives from 2.8-fold initially to 1.8-fold after phenobarbital. These results suggest that some inducing agents may be used to minimize individual variations in drug metabolism where such variations create therapeutic problems by exposing patients who slowly metabolize certain drugs to toxicity and other patients who rapidly metabolize some drugs to undertreatment.

Authors

Elliot S. Veseli, John G. Page