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.
|Number of pages||7|
|Journal||Biopharmaceutics and Drug Disposition|
|Publication status||Published - 1996|
- Crigler-Najjar syndrome type I
ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology, Toxicology and Pharmaceutics(all)