[Inhibition of cytochromes P-450. Biochemical mechanisms and possible therapeutic consequences. I--Inactivation by formation of reversible complexes].

Abstract

Inactivation of cytochrome P-450 dependent monoxygenases, a major family of hepatic oxidative drug-metabolizing enzymes, has been an area of intensive pharmacological and toxicological investigation. Several classes of drugs are known to be inducers or inhibitors of P-450 isoenzymes. The reversible inhibition of the oxidative microsomal metabolism could be directly related to the ability of the drug to bind cytochrome P-450 as shown by the formation of an inhibitory complex. Such effects result in many drug-drug interactions, affect drug disposition and drug action and could interact with the metabolism of endogenous steroids. This review is concerned primarily with a mechanistic interpretation of the reversible interactions between several classes of therapeutic agents and various P-450 isozymes. The effects of structural modifications on the inhibitory activity were also described.