Cho E, Jang S H, Lee J W, Kim N D, Lee M G
College of Pharmacy, Seoul National University, Korea.
Res Commun Mol Pathol Pharmacol. 1996 Jan;91(1):3-16.
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.
对对照组大鼠（n = 7）和预先用新型肝保护剂YH - 439处理的大鼠（200 mg/kg体重，连续3天口服给药，n = 7）静脉注射（iv）300 mg/kg体重的对乙酰氨基酚（AAP）后，研究了AAP的代谢变化。静脉注射AAP后，YH - 439处理的大鼠中AAP的AUC显著更小，AAP的CL和CLNR均显著更快。YH - 439预处理的大鼠中AAP - 葡萄糖醛酸苷的CLR以及AAP - 葡萄糖醛酸苷和AAP - 硫酸盐的部分清除率均显著更快。以AAP表示，YH - 439预处理的大鼠中在6小时胆汁中以AAP - 葡萄糖醛酸苷、AAP - 谷胱甘肽和AAP - 半胱氨酸形式排泄的静脉注射剂量百分比显著增加。上述数据表明，YH - 439预处理可增加AAP的代谢，YH - 439肝保护作用的机制似乎至少部分归因于通过增强AAP的葡萄糖醛酸化以及半胱氨酸和谷胱甘肽结合作用而增加的解毒作用。
