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  • Title: Metabolic changes of acetaminophen after intravenous administration to rats pretreated with a hepatoprotective agent, YH-439.
    Author: Cho E, Jang SH, Lee JW, Kim ND, Lee MG.
    Journal: Res Commun Mol Pathol Pharmacol; 1996 Jan; 91(1):3-16. PubMed ID: 8824927.
    Abstract:
    The metabolic changes of acetaminophen (AAP) were investigated after the intravenous (iv) administration of AAP, 300 mg per kg body weight, to the control rats (n = 7) and rats pretreated with a new hepatoprotective agent, YH-439 (200 mg per kg body weight, orally administered for 3 consecutive days, n = 7). After iv administration of AAP, the AUC of AAP was significantly smaller and both the CL and CLNR of AAP were significantly faster in the YH-439 treated rats. The CLR of AAP-glucuronide and the partial clearance of both AAP-glucuronide and AAP-sulfate were significantly faster in the YH-439 pretreated rats. The percentages of iv dose excreted in 6 hr bile as AAP-glucuronide, AAP-glutathione, and AAP-cysteine-expressed in terms of AAP-significantly increased in the YH-439 pretreated rats. The above data suggest that the metabolism of AAP increases by pretreatment with YH-439, and the mechanism for the hepatoprotective effect of YH-439 appears to be due, at least in part, to the increased detoxification by the enhanced glucuronidation, and cysteine and glutathione conjugation of AAP.
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