Vincenti F, Laskow D A, Neylan J F, Mendez R, Matas A J
Transplant Service, University of California, San Francisco, California 94143, USA.
Transplantation. 1996 Jun 15;61(11):1576-81. doi: 10.1097/00007890-199606150-00005.
Patients undergoing primary cadaveric kidney transplantation were followed for 1 year as part of a phase II, multicenter, open-label concentration-ranging trial of FK506 and cyclosporine. One hundred twenty patients were randomly assigned to a cyclosporine-based regimen or one of three FK506-based regimens designed to achieve low (5-14 ng/ml), medium (15-25 ng/ml), or high (26-40 ng/ml) trough whole blood levels. Corresponding initial doses of FK506 were 0.2, 0.3, or 0.4 mg(kg/day, respectively. Patients with toxicity to FK506 had their target concentration reduced by lowering the dose of FK506. Ninety-two patients completed a 1-year follow-up to determine patient and graft survival and long-term safety. At 1-year, the patient survival rate was 98% for FK506 and 92% for cyclosporine, and the graft survival rate was 93% and 89% in the FK506 and cyclosporine groups, respectively. The incidence of acute rejection was significantly lower (14% FK506, 32% cyclosporine, P=0.048) at day 42 after transplantation. However, the incidence of rejection episodes requiring treatment at 1 year was similar in both groups (33% for FK506 and 32% for cyclosporine). Nephrotoxicity occurred with a similar frequency with FK506 and cyclosporine, but the incidence of neurotoxic events and the incidence of new insulin use were higher among FK506-treated patients. The target range of whole blood levels that optimizes efficacy and minimizes toxicity seems to be 5-15 ng/ml. The corresponding recommended initial dose of FK506 for kidney transplant recipients is 0.2 mg/kg/day. These results indicate that the efficacy and safety of FK506 were comparable to that for cyclosporine for primary immunosuppression in patients undergoing cadaveric kidney transplantation.
作为FK506和环孢素II期多中心开放标签血药浓度范围试验的一部分，对接受初次尸体肾移植的患者进行了为期1年的随访。120例患者被随机分配至基于环孢素的治疗方案或三种基于FK506的治疗方案之一，旨在实现低（5 - 14 ng/ml）、中（15 - 25 ng/ml）或高（26 - 40 ng/ml）的谷值全血水平。FK506相应的初始剂量分别为0.2、0.3或0.4 mg/（kg·天）。对FK506产生毒性的患者通过降低FK506剂量来降低其目标浓度。92例患者完成了为期1年的随访，以确定患者和移植物的存活率以及长期安全性。1年后，FK506组患者存活率为98%，环孢素组为92%；FK506组和环孢素组的移植物存活率分别为93%和89%。移植后第42天，急性排斥反应的发生率显著降低（FK506组为14%，环孢素组为32%，P = 0.048）。然而，两组在1年时需要治疗的排斥反应发生率相似（FK506组为3%，环孢素组为32%）。FK506和环孢素导致肾毒性的频率相似，但FK506治疗的患者中神经毒性事件的发生率和新使用胰岛素的发生率更高。优化疗效并将毒性降至最低的全血水平目标范围似乎为5 - 15 ng/ml。肾移植受者FK506的相应推荐初始剂量为0.2 mg/（kg·天）。这些结果表明，在尸体肾移植患者的初次免疫抑制中，FK506的疗效和安全性与环孢素相当。
