Zonal distribution of paracetamol glucuronidation in the isolated perfused rat liver

Mack C. Mitchell, Reta Hamilton, Laura Wacker, Robert A. Branch

Research output: Contribution to journalArticle

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 100mg. 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 metabolism.

Original languageEnglish (US)
Pages (from-to)389-400
Number of pages12
JournalXenobiotica
Volume19
Issue number4
DOIs
StatePublished - 1989

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Acetaminophen
Liver
Rats
Perfusion
Recovery
Glucuronides
Metabolic Networks and Pathways
Metabolism
Pharmaceutical Preparations
Sulfates
Availability
Enzymes

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Biochemistry
  • Health, Toxicology and Mutagenesis
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Zonal distribution of paracetamol glucuronidation in the isolated perfused rat liver. / Mitchell, Mack C.; Hamilton, Reta; Wacker, Laura; Branch, Robert A.

In: Xenobiotica, Vol. 19, No. 4, 1989, p. 389-400.

Research output: Contribution to journalArticle

Mitchell, MC, Hamilton, R, Wacker, L & Branch, RA 1989, 'Zonal distribution of paracetamol glucuronidation in the isolated perfused rat liver', Xenobiotica, vol. 19, no. 4, pp. 389-400. https://doi.org/10.3109/00498258909042281
Mitchell, Mack C. ; Hamilton, Reta ; Wacker, Laura ; Branch, Robert A. / Zonal distribution of paracetamol glucuronidation in the isolated perfused rat liver. In: Xenobiotica. 1989 ; Vol. 19, No. 4. pp. 389-400.
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