Kovarik J M, Nashan B, Neuhaus P, Clavien P A, Gerbeau C, Hall M L, Korn A
Novartis Pharmaceuticals, Medizinische Hochschule, Universitäts Klinikum Rudolf Virchow, Switzerland.
Clin Pharmacol Ther. 2001 Apr;69(4):201-9. doi: 10.1067/mcp.2001.114887.
Basiliximab is a high-affinity interleukin-2 receptor (CD25) chimeric monoclonal antibody used for immunoprophylaxis in organ transplantation. It was assessed in a randomized, double-blind, placebo-controlled efficacy trial in de novo liver allograft recipients who received 40 mg of basiliximab (20 mg on days 0 and 4) in addition to baseline immunosuppression with cyclosporine (INN, ciclosporin) microemulsion and corticosteroids.
Serial blood samples (8.3 +/- 1.4 per patient) were collected during 12 weeks after transplantation from 184 basiliximab-treated patients, and empirical Bayes estimates of each patient's disposition parameters were derived. Demographic-clinical covariates were explored with regression methods.
Basiliximab clearance was 55 +/- 26 mL/h, the distribution volume was 9.7 +/- 4.2 L, and the half-life was 8.7 +/- 6.7 days. Patient weight, age, sex, ethnicity, history of alcoholism, hepatitis C seropositivity, and notable postoperative bleeding had no clinically relevant influences on basiliximab disposition; however, the cumulative volume of drained ascites fluid in the first week was positively correlated with clearance. Receptor-saturating basiliximab concentrations (> or =0.1 microg/mL) were maintained for 38 +/- 16 days, and this was negatively correlated with the cumulative volume of drained ascites fluid in week 1. Patients who experienced an acute rejection episode did not clear basiliximab at a faster rate than their rejection-free peers nor did they maintain CD25-saturating concentrations for a shorter period.
Although the standard dose regimen of 20 mg of basiliximab on days 0 and 4 after transplantation appears to be appropriate for the majority of patients with liver transplants, a supplemental dose at the end of the first week may be considered for those with substantial (>10 L) postoperative ascites fluid drainage.
巴利昔单抗是一种高亲和力的白细胞介素-2受体（CD25）嵌合单克隆抗体，用于器官移植中的免疫预防。在一项随机、双盲、安慰剂对照的疗效试验中，对初发肝移植受者进行了评估，这些受者除接受环孢素（国际非专利药品名称，环孢菌素）微乳剂和皮质类固醇进行基线免疫抑制外，还接受40mg巴利昔单抗（第0天和第4天各20mg）治疗。
在移植后的12周内，从184例接受巴利昔单抗治疗的患者中采集系列血样（每位患者8.3±1.4份），并得出每位患者处置参数的经验贝叶斯估计值。采用回归方法探讨人口统计学-临床协变量。
巴利昔单抗清除率为55±26mL/h，分布容积为9.7±4.2L，半衰期为8.7±6.7天。患者的体重、年龄、性别、种族、酗酒史、丙型肝炎血清学阳性以及显著的术后出血对巴利昔单抗的处置无临床相关影响；然而，第一周引流腹水的累积量与清除率呈正相关。受体饱和的巴利昔单抗浓度（≥0.1μg/mL）维持38±16天，这与第1周引流腹水的累积量呈负相关。发生急性排斥反应的患者清除巴利昔单抗的速度并不比未发生排斥反应的同龄人快，他们维持CD25饱和浓度的时间也没有更短。
尽管移植后第0天和第4天给予20mg巴利昔单抗的标准剂量方案似乎适用于大多数肝移植患者，但对于术后腹水引流量大（>10L）的患者，可考虑在第一周结束时给予补充剂量。
