Galinsky R E, Chałasinska B
Department of Pharmaceutics, College of Pharmacy, University of Utah, Salt Lake City 84112.
Pharm Res. 1988 Jan;5(1):61-4. doi: 10.1023/a:1015871713954.
Taurolithocholate produces a prompt, complete, and reversible cessation of bile flow in rats. This is associated with impaired hepatic oxidative drug-metabolizing activity. The purpose of this study was to examine the effects of taurolithocholate-induced cholestasis on in vivo conjugation. The pharmacokinetics of acetaminophen and the two major processes specifically responsible for its elimination, namely, the formations of acetaminophen sulfate and acetaminophen glucuronide, were used to assess hepatic conjugating activity. A 30-mg/kg bolus of acetaminophen was administered intravenously to rats 2 hr (acute cholestasis) or 20 hr (postcholestasis) after intravenous pretreatment with sodium taurolithocholate, 5 mumol/100 g body weight. Acute cholestasis increased the total clearance of acetaminophen 20%, the partial clearance to acetaminophen sulfate 12%, and the partial clearance to acetaminophen glucuronide 85%. Postcholestasis, these parameters had significantly decreased compared to those during acute cholestasis and were comparable to control values. The results show that cholestasis does not impair acetaminophen conjugation in the rat.
牛磺石胆酸盐可使大鼠胆汁流动迅速、完全且可逆地停止。这与肝脏氧化药物代谢活性受损有关。本研究的目的是研究牛磺石胆酸盐诱导的胆汁淤积对体内结合作用的影响。对乙酰氨基酚的药代动力学以及专门负责其消除的两个主要过程，即对乙酰氨基酚硫酸盐和对乙酰氨基酚葡萄糖醛酸苷的形成，被用于评估肝脏结合活性。在用5 μmol/100 g体重的牛磺石胆酸钠静脉预处理大鼠2小时（急性胆汁淤积）或20小时（胆汁淤积后）后，给大鼠静脉注射30 mg/kg的对乙酰氨基酚。急性胆汁淤积使对乙酰氨基酚的总清除率增加了20%，对乙酰氨基酚硫酸盐的部分清除率增加了12%，对乙酰氨基酚葡萄糖醛酸苷的部分清除率增加了85%。胆汁淤积后，与急性胆汁淤积期间相比，这些参数显著降低，且与对照值相当。结果表明，胆汁淤积不会损害大鼠体内对乙酰氨基酚的结合作用。
