Sonne J, Andreasen P B, Loft S, Døssing M, Andreasen F
Department of Medicine, Hvidovre Hospital, Copenhagen, Denmark.
Hepatology. 1990 Jun;11(6):951-6. doi: 10.1002/hep.1840110607.
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 less than 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 less than 0.001, in the controls. In patients with liver disease, the unbound clearance of oxazepam correlated significantly with antipyrine clearance (r = 0.88; p less than 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.
对7例失代偿期肝硬化合并肝性脑病患者和9名健康个体进行了口服奥沙西泮处置情况的研究，以进一步检验肝病时葡萄糖醛酸化保留的假说。通过安替比林清除率评估，患者的定量肝功能严重降低；中位数为9 ml·min⁻¹，范围为6至12 ml·min⁻¹。肝硬化患者奥沙西泮的表观清除率为0.55 ml·min⁻¹·kg⁻¹，范围为0.46至1.24 ml·min⁻¹·kg⁻¹，而对照组分别为1.19 ml·min⁻¹·kg⁻¹和0.80至1.66 ml·min⁻¹·kg⁻¹（p<0.05）。患者奥沙西泮的非结合清除率为4.1 ml·min⁻¹·kg⁻¹，范围为3.4至5.5 ml·min⁻¹·kg⁻¹，而对照组分别为25.4 ml·min⁻¹·kg⁻¹和16.7至43.7 ml·min⁻¹·kg⁻¹，p<0.001。在肝病患者中，奥沙西泮的非结合清除率与安替比林清除率显著相关（r = 0.88；p<0.05）。结果表明，失代偿性肝病和严重肝衰竭患者的葡萄糖醛酸化能力降低，这与定量肝功能的总体降低相一致。
