Effects of ethanol ingestion on the metabolism of a hepatotoxic dose of paracetamol in mice

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
J M TredgerR Williams

Abstract

After administration to mice of a hepatotoxic dose of paracetamol (400 mg/kg body wt, p.o.) peak plasma concentrations of the drug and its glucuronide were approximately 900 microM around one hour. Corresponding levels of the sulphate, mercapturate and cysteine conjugates were approximately 100, 35 and 20 microM, respectively. Urinary excretion accounted for 55% of the administered drug 31 h after dosing. Of this total, 64.7% was paracetamol glucuronide, 17.9% paracetamol cysteine, 10.4% paracetamol sulphate, 0.5% paracetamol mercapturate and 6.5% unchanged drug. One hour after acute ethanol administration (3 g/kg, p.o., concomitantly with paracetamol) plasma levels of the glucuronide, cysteine and mercapturate conjugates were decreased by approximately 50%. There were reductions in the urinary excretion of the glucuronide (-13%) and cysteine conjugates (-24%), but increases in the amounts of mercapturate (+52%), sulphate +11%) and unchanged drug (+81%). Chronic ethanol ingestion (15 g/kg per d for 28 d) caused a transient initial increase in plasma paracetamol cysteine (+32%) and mercapturate (+41%) concentrations, but the only substantial change in urinary excretion was a 29% increase in the amount of paracetamol glucuronide....Continue Reading

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Citations

Apr 12, 2000·British Journal of Clinical Pharmacology·L F Prescott
Sep 1, 1991·Gut·J M Tredger, M Davis
Mar 29, 2006·Clinics in Laboratory Medicine·Adam K RowdenMark A Kirk
Aug 15, 1989·Archives of Biochemistry and Biophysics·R M Hutabarat, G S Yost
Oct 18, 2005·The Medical Clinics of North America·Adam K RowdenMark A Kirk
Sep 1, 1996·Clinical Pharmacology and Therapeutics·J T SlatteryK E Thummel
May 15, 2002·Addiction Biology·Stephen M Riordan, Roger Williams
Jan 18, 2007·CNS Drug Reviews·Alfio BertoliniSheila Leone

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