title: [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.
authors.affiliation: Centre du Médicament, U.R.A. CNRS N.597, Affillié à l'INSERM, Université de Nancy I, France.
authors.forename: Z
authors.initials: Z
authors.lastname: Jayyosi
authors.forename: M H
authors.initials: MH
authors.lastname: Livertoux
authors.forename: A M
authors.initials: AM
authors.lastname: Batt
authors.forename: G
authors.initials: G
authors.lastname: Siest
mesh_terms: D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System
vernacular_title: Inhibition des cytochromes P-450. Mécanismes biochimiques et conséquences thérapeutiques éventuelles. I--Inactivation par complexation réversible.