稳定期肾移植受者使用麦考酚钠肠溶片的剂量与其暴露水平的相关性

摘要

目的 观察应用麦考酚钠肠溶片(EC-MPS)的肾移植术后6个月稳定期受者EC-MPS用量与麦考酚酸(MPA)暴露水平的相关性.方法 纳入68例受者,所有受者均采用他克莫司(Tac)、EC-MPS和泼尼松(Pred)的三联免疫抑制方案.于服用EC-MPS后1、2、4h采集外周静脉血,通过酶增强免疫分析技术测定血浆MPA浓度,以有限采样法的简化公式计算血MPA浓度-时间曲线下面积(MPA AUC).根据MPA AUC值,将受者分为MPA低暴露(MPA AUC＜30 mg·h·L-1)组,MPA目标暴露(MPA AUC=30～60 mg·h·L-1)组和MPA高暴露(MPA AUC＞60 mg·h-1·L-1)组.结果 68例受者的MPA AUC值为(58.73±20.14)mg·h·L-1,其中MPA低暴露组5例(7.35％),MPA目标暴露组35例(51.47％),MPA高暴露组28例(41.18％);3组Tac用量分别为(4.21±0.67)mg/d、(3.82±1.07)mg/d、(3.37±0.62)mg/d,呈递减趋势,MPA高暴露组Tac用量显著低于MPA低暴露组Tac用量,差异有统计学意义(P＜0.05).结论 不同受者间MPA药代动力学存在较大差异,有必要对稳定期肾移植受者EC-MPS进行监测;充足的MPA暴露有助于降低Tac的剂量,且不影响移植肾功能.%Objective To observe the association between enteric coated mycophenolate sodium (EC-MPS) dose and its exposure level at 6th month after renal transplantation in the stable recipients.Method Sixty-eight recipients were treated with tacrolimus (Tac),EC-MPS and prednisone (Pred) triple immunosuppressive regimen.Peripheral venous blood was collected at 1st,2 nd,and 4 th h after EC-MPS oral administration,and the area under concentration and time curve of MPA in the recipients were calculate by LSS formula.According to the MPA AUC value,the recipients were divided into low MPA exposure (MPA AUC ＜30 mg· h· L-1) group,MPA target exposure (MPA AUC =30-60 mg·h·L-1) group and MPA high exposure group (MPA AUC ＞60 mg·h·L-1) group.Result In 68 recipients MPA AUC was (58.73 ± 20.14) mg· h· L-1,including 5 cases (7.35 ％) in MPA low exposure group,35 cases (51.47％) in MPA target exposure group,and 28 cases (41.18％) in MPA high exposure group,respectively.Tac doses in MPA low exposure group,MPA target exposure group,and MPA high exposure group were (4.21 ± 0.67),(3.82 ± 1.07),and (3.37 ± 0.62) mg/day respectively,and showed a decreasing trend.The dosage of Tac in MPA high exposure group was significantly lower than in MPA low exposure group (P＜0.05).Conclusion There were significant differences in MPA pharmacokinetics among individuals,so it is necessary to monitor EC-MPS pharmacokinetics for stable renal transplant recipients.Adequate exposure of MPA helps to reduce the dose of Tac,and does not influence the renal graft function.