EXOGENOUS HEME RESTORES INVIVO FUNCTIONAL-CAPACITY OF HEPATIC CYTOCHROME-P-450 DESTROYED BY ALLYLISOPROPYLACETAMIDE

Administration of allylisopropylacetamide (AIA) produces a dose-related destruction of the heme moiety of the phenobarbital-induced subspecies of hepatic cytochrome P-450 causing delayed plasma disappearance of the inactivating agent as determined after injection of [14C]AIA. In phenobarbital-pretreated rats, infusion of heme reversed this AIA-mediated impairment of the plasma disappearance of [14C]AIA. In the absence of phenobarbital pretreatment, cytochrome P-450 destruction by AIA was minimal and heme infusion failed to enhance plasma disappearance of [14C]AIA. Exogenously administered heme is incorporated into hepatic cytochrome P-450 in vivo; apparently the infused heme restored the functional capacity of the phenobarbital-induced mixed function oxidase system by substituting for the prosthetic heme moiety destroyed by AIA. Heme infusion is a potentially useful therapeutic modality for enhancing drug biotransformation after intoxication with compounds that inactivate cytochrome P-450.