Glucuronidation of diflunisal, (-)- morphine, 4-nitrophenol, and propofol in liver microsomes of two patients with Crigler-Najjar syndrome type I

Françoise M. Brunelle, Araz A. Raoof, Jean De Ville De Goyet, Roger K. Verbeeck

Research output: Contribution to journalArticle

Abstract

In vitro glucuronidation was studied in liver microsomes from two patients with Crigler-Najjar type I (CN-I) disease and compared with the activity measured in microsomes prepared from six control human livers. The UDP-glucuronosyltransferase (UGT) activity was determined toward the following substrates: 4-nitrophenol, propofol, (-)-morphine (formation of the 3-glucuronide), and diflunisal (formation of the phenolic and acyl glucuronides). Glucuronidation of 4-nitrophenol was reduced in one of the CN-I livers (CN-I No. 1) (0.9 nmol min-1 mg-1) and normal in the other CN-I liver (CN-I No. 2) (3.5 nmol min-1 mg-1) compared to the control livers (5.6±2.9 nmol min-1 mg-1, mean ±S.D.). Propofol glucuronidation was not detectable (i.e. less than 0.100 nmol min-1 mg-1) in the CN-I No. 1 liver and normal in the CN-I No. 2 liver (l.78 nmol min-1 mg-1 against 1.52 ±0-72 nmol min-1 mg-1 in the control livers). The glucuronidation of (-)-morphine to the 3-glucuronide and the formation of the phenolic and acyl glucuronides of diflunisal were normal in both CN-I livers compared to the control livers. Our results show that CN-I patients are heterogeneous regarding UGT activity toward the phenolic substances 4-nitrophenol and propofol.

Original languageEnglish
Pages (from-to)311-317
Number of pages7
JournalBiopharmaceutics and Drug Disposition
Volume17
Issue number4
Publication statusPublished - 1996

Keywords

  • (-)-morphine
  • 4-nitrophenol
  • Crigler-Najjar syndrome type I
  • Diflunisal
  • Propofol
  • UDP-glucuronosyltransferase

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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