INTERACTION OF THE ENZYME INDUCER, HOE 17,879, WITH MICROSOMAL ENZYME SYSTEMS

Abstract

Publisher Summary The aliphatic amide, 2–hydroxy–2–ethylbutyryl N, N–diethyl–amide (HOE 17,879), has no remarkable pharmacological effect but acts on hepatic drug-metabolizing enzymes and on drug action times in a biphasic way depending on the time schedule of administration. After initial enzyme inhibition, enzyme induction occurs. This chapter discusses the effects of HOE 17,879 on the hepatic microsomal drug-metabolizing enzyme systems in vitro. HOE 17,879 does not inhibit microsomal, nicotinamide adenine dinucleotide phosphate-oxidase (NADPH)–specific cytochrome c, neotetrazolium reductases, or methylumbelliferone glucuronyltransferase. With rat liver microsomes, HOE 17,879 gives a type I cytochrome substrate difference spectrum. Therefore, the inhibition of the mixed-function oxidases is because of an interaction of HOE 17,879 with cytochrome P-450 at the substrate-binding site and not with the microsomal reductase or the microsomal glucuronyl transferase.