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  • Title: Effect of taurolithocholate on in vivo sulfation and glucuronidation of acetaminophen in rats.
    Author: Galinsky RE, Chałasinska B.
    Journal: Pharm Res; 1988 Jan; 5(1):61-4. PubMed ID: 3244612.
    Abstract:
    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.
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