Bower S, Sear J W, Roy R C, Carter R F
Department of Anaesthetics, University of Newcastle upon Tyne.
Br J Anaesth. 1992 May;68(5):462-5. doi: 10.1093/bja/68.5.462.
We have studied the influence of different hepatic pathologies on the disposition of alfentanil in 23 unpremedicated patients (six healthy control subjects, six patients with liver dysfunction of alcoholic aetiology and 11 patients with non-alcohol related liver disease). All patients received a bolus of alfentanil 500 micrograms i.v. as supplement to 67% nitrous oxide and isoflurane in oxygen anaesthesia. Plasma drug concentrations were measured in venous blood samples at intervals up to 24 h by radio-immunoassay and protein binding was determined by equilibrium dialysis. Kinetic estimates were determined using non-compartmental analysis. Patients with non-alcoholic liver disease had lesser plasma clearance (114.8 (range 66.8-213.5) ml min-1) than the alcoholic group (158.8 (100.0-220.7) ml min-1) or controls (187.4 (125.2-269.5) ml min-1). In all three groups, there was considerable intersubject variability, with a bimodal distribution in the non-alcoholic group. This group also had a smaller apparent volume of distribution at steady state. Mean residence time was prolonged in the alcoholic group compared with controls (284.9 (217.8-362.2) min vs 226.8 (201.2-250) min). Protein binding was decreased in the alcoholic group compared with controls (84.9 (SD 4.2)% vs 89.3 (2.1)%); this was attributable to a lesser plasma alpha 1-acid glycoprotein concentration (0.55 (0.18) g litre-1 vs 0.89 (0.21) g litre-1). Free drug clearance was reduced in both liver dysfunction groups compared with controls.
我们研究了23例未用术前药患者（6例健康对照者、6例酒精性病因所致肝功能不全患者和11例非酒精相关性肝病患者）中不同肝脏病变对阿芬太尼处置的影响。所有患者静脉注射500微克阿芬太尼推注量，作为67%氧化亚氮和异氟烷在氧气中麻醉的补充。通过放射免疫分析法在长达24小时的间隔时间测定静脉血样中的血浆药物浓度，并通过平衡透析法测定蛋白结合率。使用非房室分析确定动力学估计值。非酒精性肝病患者的血浆清除率（114.8（范围66.8 - 213.5）毫升/分钟）低于酒精性组（158.8（100.0 - 220.7）毫升/分钟）或对照组（187.4（125.2 - 269.5）毫升/分钟）。在所有三组中，个体间存在相当大的变异性，非酒精性组呈双峰分布。该组在稳态时的表观分布容积也较小。与对照组相比，酒精性组的平均驻留时间延长（284.9（217.8 - 362.2）分钟对226.8（201.2 - 250）分钟）。与对照组相比，酒精性组的蛋白结合率降低（84.9（标准差4.2）%对89.3（2.1）%）；这归因于血浆α1 - 酸性糖蛋白浓度较低（0.55（0.18）克/升对0.89（0.21）克/升）。与对照组相比，两个肝功能不全组的游离药物清除率均降低。
