prevention of Acetaminophen and Cocaine Hepatotoxicity in Mice by Cimetidine Treatment

摘要: Hepatotoxicity occurs in animals after administration of large doses acetaminophen and cocaine is thought to result from production reactive metabolites these parent drugs by cytochrome P450. Because cimetidine binds P450 inhibits hepatic drug metabolism both humans animals, we determined the effects coadministration on hepatotoxicity mice. Marked elevations serum glutamic pyruvic transaminase severe pericentral hepatocellular necrosis occurred receiving intraperitoneal 350 mg/kg or 35 cocaine, while minimal liver were seen who also received 100 1 h before either cocaine. Consistent with hypothesis that vivo protective resulted interaction P450, inhibited vitro microsomal However, despite its effect against acetaminophen-induced injury, concomitant did not significantly affect plasma pharmacokinetics acetaminophen, prevent depletion glutathione administration, alter covalent binding [3H]acetaminophen proteins. These studies suggest current theories regarding damage require reexamination. The possibility treatment might be useful preventing due other hepatotoxins intriguing warrants consideration.