The glutathione-linked metabolism of 2-allyl-2-isopropy-lacetamide in rats. Further evidence for the formation of a reactive metabolite

2-Allyl-2-isopropylacetamide (AIA) causes a depletion of liver glutathione in rats only if the animals have been pretreated with phenobarbitone. Phenobarbitone stimulates the excretion in bile of a component derived from AIA and glutathione which is apparently not the same as the conjugate formed by reaction of the two components in simple solutions. The significance of these findings are considered in relation to the suggestion that AIA is metabolised to an epoxide by the microsomal enzyme system; in addition several differences between AIA and the non-porphyrogenic compound, acrylamide, are discussed.