Premium
Glucuronidation of oxazepam is not spared in patients with hepatic encephalopathy
Author(s) -
Sonne Jesper,
Andreasen Per Buch,
Loft Steffen,
Døsing Martin,
Andreasen Frederik
Publication year - 1990
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840110607
Subject(s) - oxazepam , glucuronidation , medicine , cirrhosis , hepatic encephalopathy , hepatology , liver disease , pharmacokinetics , liver function , gastroenterology , metabolite , endocrinology , chemistry , benzodiazepine , in vitro , microsome , biochemistry , receptor
The disposition of oral oxazepam was investigated in seven patients with decompensated cirrhosis and encephalopathy and in nine healthy individuals to further examine the hypothesis of preservation of glucuronidation in liver disease. The patients showed a severe reduction in the quantitative liver function as assessed by estimation of the clearance of antipyrine; the median value was 9 ml. min −1 and the range was 6 to 12 ml. min −1 . Apparent clearance of oxazepam in cirrhotic patients was 0.55 ml. min −1 . kg −1 , with a range of 0.46 to 1.24 ml. min −1 . kg −1 , compared with 1.19 ml. min −1 . kg −1 and a range of 0.80 to 1.66 ml. min −1 . kg −1 in the controls (p < 0.05). The unbound clearance of oxazepam in patients was 4.1 ml. min −1 . kg −1 , with a range of 3.4 to 5.5 ml. min −1 . kg −1 , compared with 25.4 ml. min −1 . kg −1 , and a range of 16.7 to 43.7 ml. min −1 , kg −1 , p < 0.001, in the controls. In patients with liver disease, the unbound clearance of oxazepam correlated significantly with antiyprine clearance (r = 0.88; p < 0.05). The results suggest a reduced capacity for glucuronidation in patients with decompensated liver disease and severe hepatic failure that corresponds to the general reduction in the quantitative liver function.(HEPATOLOGY 1990;11:951‐956.).