Jochemsen R, Joeres R P, Wesselman J G, Richter E, Breimer D D
Br J Clin Pharmacol. 1983;16 Suppl 2(Suppl 2):315S-322S. doi: 10.1111/j.1365-2125.1983.tb02306.x.
Disposition of oral brotizolam (0.5 mg) was studied in male patients with liver cirrhosis (patients) and in other patients (control) matched for age, weight, smoking and drinking habits. Absorption of brotizolam was relatively rapid in both groups with a median peak time (range) of 1.0 (0.5-2.0) h. Peak concentrations were also similar with median values of 7.1 (3.2-10.7) ng/ml in patients and 9.4 (2.9-19.0 ng/ml) in controls. Elimination half-life was longer in patients than in controls. The median values were 12.8 (9.4-25) h and 6.9 (4.4-8.4) h respectively (P less than 0.01). In two patients hardly any drug elimination was observed, indicating severe impairment of drug metabolizing activity. The prolongation of the elimination half-life was likely to be due to a decrease in clearance (45 ml/min in patients compared with 64 ml/min in controls), and an increase in volume of distribution (0.62 l/kg and 0.39 l/kg respectively). Median values of protein unbound fraction of brotizolam were 9.2 (7.8-10.4) % in controls and 12.4 (10.4-18.9) % in patients. Clearance of unbound drug was 612 ml/min and 380 ml/min respectively.
对患有肝硬化的男性患者（患者组）以及年龄、体重、吸烟和饮酒习惯相匹配的其他患者（对照组），研究了口服溴替唑仑（0.5毫克）的处置情况。两组中溴替唑仑的吸收相对较快，中位达峰时间（范围）为1.0（0.5 - 2.0）小时。峰浓度也相似，患者组中位值为7.1（3.2 - 10.7）纳克/毫升，对照组为9.4（2.9 - 19.0）纳克/毫升。患者组的消除半衰期比对照组更长。中位值分别为12.8（9.4 - 25）小时和6.9（4.4 - 8.4）小时（P小于0.01）。在两名患者中几乎未观察到药物消除，表明药物代谢活性严重受损。消除半衰期的延长可能是由于清除率降低（患者组为45毫升/分钟，对照组为64毫升/分钟）以及分布容积增加（分别为0.62升/千克和0.39升/千克）。溴替唑仑蛋白未结合分数的中位值在对照组为9.2（7.8 - 10.4）%，在患者组为12.4（10.4 - 18.9）%。未结合药物的清除率分别为612毫升/分钟和380毫升/分钟。
