Metabolic changes of acetaminophen after intravenous administration to rats pretreated with a hepatoprotective agent, YH-439.

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.

• Authors: E Cho, S H Jang, J W Lee, N D Kim, M G Lee
• Journal: Research communications in molecular pathology and pharmacology (Res Commun Mol Pathol Pharmacol) Vol. 91 Issue 1 Pg. 3-16 (Jan 1996) ISSN: 1078-0297 [Print] United States
• PMID: 8824927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Non-Narcotic
• Thiazoles
• YH 439
• Acetaminophen

Topics

• Acetaminophen (administration & dosage, metabolism)
• Analgesics, Non-Narcotic (metabolism)
• Animals
• Bile (metabolism)
• Half-Life
• Injections, Intravenous
• Liver (drug effects)
• Metabolic Clearance Rate
• Rats
• Rats, Sprague-Dawley
• Thiazoles (pharmacology)