Sep 3, 1976

Isoniazid and iproniazid: activation of metabolites to toxic intermediates in man and rat

Science
S D NelsonG B Corcoran

Abstract

Acetylhydrazine, a metabolite of isoniazid, a widely used antituberculosis drug, and isopropylhydrazine, a metabolite of iproniazid, an antidepressant removed from clinical use because of high incidence of liver injury, were oxidized by cytochrome P-450 enzymes in human and rat liver microsomes to highly reactive acylating and alkylating agents. Covalent binding of these metabolites to liver macromolecules paralleled hepatic cellular necrosis. The metabolites formed from these and probably other monosubstituted hydrazines are reactive electrophiles.

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Mentioned in this Paper

Necrosis
Covalent Interaction
Enzymes, antithrombotic
Structure-Activity Relationship
Cytochrome P450
Hepatic
Drug-Induced Acute Liver Injury
Hydrazines
Microsomes, Liver
Iproniazid

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