GLUCURONIDATION OF DIFLUNISAL, (−)-MORPHINE, 4-NITROPHENOL, AND PROPOFOL IN LIVER MICROSOMES OF TWO PATIENTS WITH CRIGLER–NAJJAR SYNDROME TYPE I
✍ Scribed by Françoise M. Brunelle; Araz A. Raoof; Jean De Ville De Goyet; Roger K. Verbeeck
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 403 KB
- Volume
- 17
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
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) (0.9nmolmin-I mg-') and normal in the other CN-I liver (CN-I No. 2) (3.5 nmolmin-'mg-l) compared to the control livers (5.6 * 2.9 nmolmin-' mg-', mean f S.D.). Propofol glucuronidation was not detectable (i.e. less than O.lOOnmolmin-l mg-') in the CN-I No. 1 liver and normal in the CN-I No.2liver (1.78nmolrnin-'mg-' against 1~521k0~72nmolmin-'mg-' 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.