西罗莫司治疗肾移植后排斥反应的疗效、不良反应与其血药浓度的相关性分析

Correlation between Therapeutic Efficacy,Adverse Drug Reaction and Plasma Concentration of Sirolimus in the Treatment of Reject Reaction after Renal Transplantation

目的:观察西罗莫司治疗肾移植后排斥反应时,其疗效、不良反应与血药浓度的相关性。方法:选择52名肾移植术后应用西罗莫司进行免疫抑制治疗的患者为研究对象,其中男性43人,女性9人。采用高效液相色谱(HPLC)法测定西罗莫司血药浓度,同时测定患者的肌酐清除率、肝功能指标、血常规等。结果:共收集西罗莫司血药浓度数据112份。西罗莫司的血药浓度与给药剂量/体重比呈正相关,与体重呈负相关,女性患者血药浓度明显高于男性患者(P<0.05),未发现西罗莫司血药浓度与年龄有明显相关性;西罗莫司的主要不良反应表现为肝功能损伤,将血药浓度分为<8ng·mL-1和>8ng·mL-1组,不同血药浓度组的肝功能差异有统计学意义(P<0.05);西罗莫司的临床疗效确切,将西罗莫司稳态谷浓度分成<4ng·mL-1、4～8ng·mL-1和>8ng·mL-1组,不同血药浓度组其肌酐清除率和肾功能恢复情况差异有统计学意义(P<0.05)。结论:西罗莫司副作用主要表现为肝功能异常,其血药浓度与临床疗效和不良反应均有相关性,西罗莫司稳态谷浓度宜控制在4～8ng·mL-1范围内。

OBJECTIVE：To observe the correlation between therapeutic efficacy,adverse drug reaction and plasma concentration of sirolimus in the treatment of reject reaction after renal transplantation.METHODS：52 renal transplantation patients including 43 males and 9 females were included to our study,who received sirolimus for antirejection therapy after operation.HPLC was used to determine sirolimus concentration.Creatinine clearance rate,liver function index and blood routine were tested.RESULTS：The data of 112 samples of sirolimus concentration were collected and analyzed.Sirolimus concentration had positive correlation with the ratio of dosage to weight,negative correlation with weight,no correlation with age.Sirolimus concentration in female patients was significantly higher than in male.The main adverse drug reaction of sirolimus was impairment of liver function.Statistical difference of liver function was found between two different concentration groups （P0.05）,which were 8 ng·mL-1 group and 8 ng·mL-1 group.Therapeutic effect of sirolimus was obvious.Statistical differences of creatinine clearance rate and recovery of renal function were found in three different groups according to the steady trough concentration of sirolimus （P0.05）,which were 4 ng·mL-11 group,4～8 ng·mL-1 group and 8 ng·mL-1 group.CONCLUSION：The main side-effect of sirolimus is impairment of liver function.The plasma concentration of sirolimus has correlation with clinical efficacy and adverse drug reaction,and the steady trough concentration should be controlled at the range of 4～8 ng·mL-1.