Yee G C, Kennedy M S, Storb R, Thomas E D
Blood. 1984 Dec;64(6):1277-9.
The effect of hepatic dysfunction, defined as abnormal serum bilirubin level, on oral cyclosporin (CSP) pharmacokinetics was examined in 28 marrow transplant patients who received CSP for prophylaxis of graft-v-host disease. Serum CSP concentrations were measured by radioimmunoassay. Forty-one concentration-time courses were studied, divided among patients with no (less than 1.2 mg/dL), mild (1.2 to 2.0 mg/dL), and moderate (2.0 to 5.0 mg/dL) hepatic dysfunction. CSP elimination, as determined by elimination rate constant and clearance, was delayed in patients with moderate hepatic dysfunction compared to those with no hepatic dysfunction (P less than .05). The volume of distribution, lag time for absorption, maximum serum concentration, and time at which the maximum concentration was achieved was not affected by hepatic function. These data indicate that patients with moderate hepatic dysfunction have delayed CSP or CSP metabolite elimination and may be at higher risk for developing CSP-related toxicity.
在28例接受环孢素（CSP）预防移植物抗宿主病的骨髓移植患者中，研究了定义为血清胆红素水平异常的肝功能障碍对口服CSP药代动力学的影响。通过放射免疫测定法测量血清CSP浓度。研究了41个浓度-时间过程，这些过程分布在无肝功能障碍（低于1.2mg/dL）、轻度肝功能障碍（1.2至2.0mg/dL）和中度肝功能障碍（2.0至5.0mg/dL）的患者中。与无肝功能障碍的患者相比，中度肝功能障碍患者中由消除速率常数和清除率所确定的CSP消除延迟（P<0.05）。分布容积、吸收滞后时间、最大血清浓度以及达到最大浓度的时间不受肝功能影响。这些数据表明，中度肝功能障碍患者的CSP或CSP代谢产物消除延迟，可能发生CSP相关毒性的风险更高。
