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  • Title: Isoniazid and iproniazid: activation of metabolites to toxic intermediates in man and rat.
    Author: Nelson SD, Mitchell JR, Timbrell JA, Snodgrass WR, Corcoran GB.
    Journal: Science; 1976 Sep 03; 193(4256):901-3. PubMed ID: 7838.
    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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