Phenobarbital-induced drug metabolism in man

Abstract

Phenobarbital and antipyrine half-lives were measured in 31 subjects. A high correlation ( r = 0.87) was found for the plasma elimination rates of the two drugs, suggesting the same or a similar route or a common regulatory control of their metabolism. The half-lives of phenobarbital and antipyrine also correlated highly with the aryl hydrocarbon hydroxylase (AHH) inducibilities in mitogen-stimulated lymphocytes of the same individuals. In the second part of the study, plasma antipyrine half-lives were measured in 22 subjects after a single oral dose of 18 mg/kg, and the AHH inducibilities were determined in their cultured lymphocytes. After 7 days on phenobarbital at aryl hydrocarbon hydroxylase inducibilityadjusted doses ranging between 1.0 and 2.0 mg/kg daily, the antipyrine half-lives were measured again and the percentage of decrease between the initial and second antipyrine half-lives was determined. Shortening of the plasma half-lives occurred in all subjects to various degrees, ranging between 13.3 and 30.6%. However, under our experimental conditions in which the dose of phenobarbital was adjusted to the individual rates of metabolism of the inducing agent, no relationship could be found between the initial antipyrine half-life and the percentage of shortening of its plasma half-life, such as had been reported by several authors.