Glucuronidation of Oxazepam Is Not Spared in Patients With Hepatic Encephalopathy

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Abstract
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.).

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