PMID: 2501939Apr 1, 1989Paper

Zonal distribution of paracetamol glucuronidation in the isolated perfused rat liver

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
M C MitchellR A Branch

Abstract

1. The lobular distribution of paracetamol conjugation was studied using antegrade and retrograde perfusion of isolated rat liver. After addition of 25 mg of paracetamol, recovery of sulphate from antegrade perfusions was greater than from retrograde perfusions indicating periportal predominance of this metabolic pathway. 2. Recovery of sulphate was greater than recovery of glucuronide after addition of 25 mg of paracetamol during both antegrade and retrograde perfusions. Recovery of sulphate was similar after addition of 25 or 100 mg of paracetamol, whereas recovery of the glucuronide was increased at the higher dose, indicating a higher capacity for glucuronidation than for sulphation, but a higher affinity for sulphation. 3. Recovery of glucuronide from antegrade and retrograde perfusions was similar after addition of 25 mg of paracetamol, but was greater from antegrade perfusions after addition of 100 mg. This indicates that drug concentration may be an important determinant of the zonal distribution of drug metabolism. Factors other than localization of drug-metabolizing enzymes, such as competition with other metabolic pathways or availability of cofactors, may also influence the apparent zonal distribution of drug metabo...Continue Reading

References

Apr 1, 1977·The Journal of Pharmacy and Pharmacology·D HowieL F Prescott
Mar 1, 1978·The American Journal of Physiology·J J GumucioM Keener
Dec 25, 1978·Life Sciences·J BaronF P Guengerich
May 1, 1986·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M el Mouelhi, F C Kauffman
Jul 1, 1984·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·V F Price, D J Jollow
Jul 1, 1983·Clinical Pharmacology and Therapeutics·M C MitchellS Schenker
Dec 7, 1981·Life Sciences·M D Green, L J Fischer
Jan 1, 1981·Advances in Experimental Medicine and Biology·D J JollowC Smith

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Citations

Apr 1, 1991·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A M Hoyumpa, S Schenker
Dec 9, 2014·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·K E HulseR P Schleimer
Jul 1, 1995·The American Journal of Physiology·B R LandauH Brunengraber

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