足叶乙甙在血液透析患者中的应用研究

Application Study of Etoposide in the Patients with Haemodialysis

目的通过检测足叶乙甙浓度及其药代动力学参数,对血液透析治疗的患者应用标准剂量的足叶乙甙进行药物安全性研究。方法通过高效液相色谱法,检测血浆中足叶乙甙浓度(总浓度和非蛋白结合浓度),观察患者在透析前后药物的浓度、半衰期、药物分布容积等指标。结果足叶乙甙的透析前后药物半衰期的对比符合一级动力两室模型,15例患者透析前后足叶乙甙的半衰期t1/2分别为:(4.3±0.45)h,(3.5±0.36)h。透析过程中药物分布容积为(8.5±0.4)L/m2,血液中非蛋白结合状态的足叶乙甙占总浓度的9.0%(9.02%±0.7%)。结论在有肾功能损害的情况下,足叶乙甙在体内通过排泄途径的改变使药物的清除率无明显下降,血透治疗没有显著增加足叶乙甙的排泄。在药动学和临床治疗反应的动态监测下,标准剂量的足叶乙甙静脉治疗在取得积极疗效的同时,药物不良反应轻微,具有较好的安全性。

Objective To study the safety of standard dosing of etoposide for haemodialysis patients when pharmacokinetics monitoring is applicable. Method Using High Performance Liquid Chromatography, the concentrations of etoposidc, half life （t1/2） ,and volume of distribution （Vd） in serum were determined and analyzed. Result 15 patients were examined in this study. The kinetics of etoposide elimination during haemodialysis was compatible with the first order two-compartment model. The T1/2 of etoposide before and after haemodialysis was （4.3± 0.45）h and （3.5±0.36）h, respectively. The Vd was （8.5±0.4）L/m： and the free etoposide fraction were 9.0% （9.02%±0.7%）. Conclusion Under the condition of severe renal dysfunction, the elimination of etoposide was not obviously decreased. Haemodialysis did not increase the elimination of etoposide significantly. To achieve a desirable effect and a mild side effect, a standard dose of etoposide may be applied to patients on dialysis.