摘要
目的 研究发生环孢素A(CsA)肝损害的肾移植患者口服CsA胶囊的药代动力学特点及意义。方法 测定 32例服用CsA胶囊后发生肝功能异常者的血CsA浓度谷值 (C0 )及峰值(Cmax)、达到峰值的时间 (Tmax)、浓度时间曲线下面积 (AUC)及CsA清除率 (CI) ,统计出现CsA肝损害的时间、肝功能异常的程度、CsA的用量 ,并针对肝功能异常程度的不同给予不同的治疗方案 ;以30例肝功能正常的肾移植患者作对照。结果 随着肝功能异常程度的加重 ,C0 有明显上升的趋势 ,Cmax有明显下降的趋势 ,Tmax明显延长 ,中、重度肝功能异常者的C0 与AUC的相关性差 ;对轻度肝功能异常者 ,可根据其CsA的AUC适当减少CsA的用量 ,而中、重度肝功能异常患者 ,治疗时应增加其它肝毒性较小的免疫抑制剂的用量 ,并根据其CsA的AUC将CsA的用量减少 1/ 3～ 1/ 2 ,甚至停用CsA ,改为肝毒性较小的药物。结论 发生CsA肝损害的患者 ,其CsA药代动力学与肝功能正常者相比 ,差异有显著性 ;中、重度肝功能异常患者需定期监测CsA的AUC 。
Objectives To study pharmacokinetics and pharmacodynamic of cyclosporine (CsA) in renal transplant recipients with hepatotoxicity, and establish a management strategy of CsA dose reduction. Methods Thirty patients were collected from a total of 308 patients receiving renal allografts under immunosuppression of CsA/azathioporine/prednisone and 32 patients who experienced at least one episode of posttransplant hepatotoxicity. Pharmacokinetic (incuding C 0, C max , T max , AUC and CI), clinical and renal function parameters were measured in all the 32 patients. Results When the patients with moderate or severe hepatotoxicity were compared with those normal patients, C 0 was higher, T max was longer, and C max and CI were significantly decreased. When hepatotoxicity was not serious, the management strategy of CsA dose reduction was effective. When the patients with severe hepatotoxicity, CsA should be replaced by other immmunosuppressants with less hepatotoxicity, such as FK506. Conclusions There was a significant difference in CsA pharmacokinetic parameters between the patients with hepatotoxicity and normal patients . The management strategy should be individualized.
出处
《中华器官移植杂志》
CAS
CSCD
北大核心
2001年第1期17-19,共3页
Chinese Journal of Organ Transplantation
