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GLUCURONIDATION OF DIFLUNISAL, (−)‐MORPHINE, 4‐NITROPHENOL, AND PROPOFOL IN LIVER MICROSOMES OF TWO PATIENTS WITH CRIGLER–NAJJAR SYNDROME TYPE I
Author(s) -
Brunelle Françoise M.,
Raoof Araz A.,
De Ville De Goyet Jean,
Verbeeck Roger K.
Publication year - 1996
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199605)17:4<311::aid-bdd953>3.0.co;2-v
Subject(s) - glucuronidation , diflunisal , chemistry , microsome , glucuronide , microsoma , bilirubin , glucuronosyltransferase , nitrophenol , propofol , pharmacology , endocrinology , medicine , metabolism , biochemistry , in vitro , catalysis
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 (1·78 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.