Metabolic changes of acetaminophen after intravenous administration to rats pretreated with a hepatoprotective agent, YH-439.
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.
Cho
E
E
College of Pharmacy, Seoul National University, Korea.
Jang
S H
SH
Lee
J W
JW
Kim
N D
ND
Lee
M G
MG
D000082:Acetaminophen / Q000008:administration & dosage / Q000378:metabolism*; D018712:Analgesics, Non-Narcotic / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000378:metabolism; D006207:Half-Life; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects*; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology*
D018712:Analgesics, Non-Narcotic; D013844:Thiazoles; C098009:YH 439; D000082:Acetaminophen