Destruction of endogenous and exogenous haem by 2-allyl-2-isopropylacetamide: Role of the liver cytochrome p-450 which is inducible by phenobarbitone

Abstract

1. 1. The study of the kinetics of cytochrome P-450 loss caused by 2-allyl-2-isopropylacetamide in vivo showed the existence of at least two components: pre-treatment with phenobarbitone markedly increased the amount of the fast decaying component without altering its half-life, but did not change significantly either amount or half-life of the slow decaying component. 2. 2. It is suggested (i) that the two components represent different cytochromes which are destroyed at different rates by 2-allyl-2-isopropylacetamide; and (ii) that phenobarbitone pre-treatment stimulates the destruction of cytochrome P-450 by increasing the concentration in the microsomal fraction of the type of cytochrome which is susceptible to rapid destruction. 3. 3. Exogenous haem was also destroyed when the liver microsomal fraction was incubated with the drug in vitro. This suggests that the action of the drug is not confined to the haem of the preexisting cytochrome P-450 but may extend to other pools of haem in the liver.