肾移植受者应用西罗莫司治疗窗的临床研究

目的:探讨西罗莫司应用于国内肾移植受者的治疗窗范围。方法:采用多中心、开放性临床研究,来自国内4家移植中心的首次肾移植病人共100例。免疫抑制方案为西罗莫司联合环孢素和皮质激素的三联疗法。移植后48h内开始服用西罗莫司,首次负荷剂量为6mg·d-1,维持剂量为2mg·d-1,采用高效液相色谱法测定西罗莫司浓度。结果:100例病人西罗莫司总的全血谷浓度为(6.6±s2.8)μg·L-1,10及90百分位数浓度分别为3.2μg·L-1和10.26μg·L-1。肾移植后6mo内急性排斥发生率为10%(8/84),此8例病人急性排斥时的西罗莫司浓度明显低于非排斥时浓度(P<0.01)。主要不良反应为肝功能损害和高脂血症,三酰甘油浓度与西罗莫司浓度相关(r=0.276,P<0.01)。结论:西罗莫司浓度维持在4～8μg·L-1范围内较为合适,定期监测血药浓度,合理调整用量,可增加西罗莫司应用的有效性及安全性。

Therapeutic window of whole-blood sirolimus concentration in kidney transplantation recipient

AIM: To study the therapeutic window of sirolimus concentration in Chinese kidney transplantation recipient. METHODS: An open-label, multi-center study included 100 primary renal allograft recipients enrolled from 4 transplantation centers in China. The immunosuppressive therapy consisted of triple regimens, i.e. sirolimus combining with ciclosporin and steroids. A loading dose of sirolimus 6 mg was administered within 48 h after the transplantation and then a maintaining dose of 2 mg·d -1 was administered. The whole blood concentration of sirolimus was measured by high performance liquid chromatography. RESULTS: The whole blood concentration of sirolimus in this group was (6.6±s 2.8) μg·L -1. The 10 th and 90 th percentiles for sirolimus concentration were 3.2 μg·L -1 and 10.26 μg·L -1, respectively. 9.5 % (8/84) patients suffered from acute rejection within 6 mo period after transplantation in this study, and the concentration of sirolimus in such patients was lower than non-rejection patients (P< 0.01). Hyperlipidemia and liver dysfunction were the most frequent adverse reactions, and sirolimus concentration was significantly associated with the concentration of triglyceride (P< 0.01). CONCLUSION: Four to eight μg·L -1 is a suitable level for sirolimus concentration in Chinese kidney transplantation recipient patients. Regular drug monitoring and reasonably dose modulation may increase the validity and security of sirolimus application.