肾移植受者免疫抑制维持治疗期霉酚酸酯剂量与霉酚酸暴露的关系

Relationship between mycophenolate mofetil dose and mycophenolate acid exposure in renal allograft recipients during maintenance immunosuppressive therapy

目的观察服用霉酚酸酯(MMF)的肾移植受者在免疫抑制维持治疗期霉酚酸(MPA)的暴露水平。方法 60例肾移植受者均采用环孢素A(CsA)、MMF和强的松(Pred)三联免疫抑制方案,于服用MMF后0.5、2、4 h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肾移植受者MPA血药浓度—时间曲线下面积(AUC)。根据口服MMF剂量,将患者分为3组:MMF低剂量组(MMF<1.5 g/d,n=18)、MMF推荐剂量组(MMF=1.5 g/d,n=29)、MMF高剂量组(MMF>1.5 g/d,n=13)。根据MPA AUC值,将患者分为MPA低暴露组(MPA AUC<30 mg.h.L-1)、MPA目标暴露组(MPAAUC=30～60 mg.h.L-1)、MPA高暴露组(MPA AUC>60 mg.h.L-1)。结果 60例肾移植受者MPA AUC平均值为(59.83±19.42)mg.h.L-1;其中,MPA低暴露组3例(5.0%),MPA目标暴露组31例(51.7%),MPA高暴露组26例(43.3%);三组CsA平均用量分别为(166.67±14.43)mg/d、(137.10±41.27)mg/d和(128.85±37.88)mg/d,呈递减趋势,但组间差异无统计学意义(P>0.05)。结论在未监测MPA AUC水平而仅根据临床事件调整MMF用量的情况下,肾移植受者平均MPA暴露水平偏高;MPA药代动力学在不同个体间存在较大的差异,进行MMF的治疗药物监测可能是必要的。

Objective To investigate the level of mycophenolate acid（MPA） exposure in renal allograft recipients receiving mycophenolate mofetil（MMF） as maintenance immunosuppressive therapy.Methods Sixty renal allograft recipients were treated with cyclosporine A（CsA）,MMF and prednisone（Pred）,peripheral vein blood samples were obtained 0.5 h,2 h and 4 h after administration of MMF,the plasma concentrations of MPA were measured by enzyme-multiplied immunoassay technique.The values of area under the curve（AUC） of plasma MPA concentration（MPA AUC） of the renal allograft recipients were calculated by the simplified formula of limited sampling strategy.All recipients were divided into low dose MMF group（MMF〈1.5 g/d,n=18）,recommendation dose group（MMF=1.5 g/d,n=29） and high dose MMF group（MMF〉1.5 g/d,n=13） according to doses of oral administration of MMF.Besides,all recipients were divided into low exposure to MPA group（MPA AUC〈30 mg·h·L-1）,target exposure to MPA group（MPA AUC= 30-60 mg·h·L-1） and high exposure to MPA group（MPA AUC〉60 mg·h·L-1） according to values of MPA AUC.Results The mean MPA AUC of 60 renal transplant recipients was（59.83±19.42） mg·h·L-1.There were 3 cases（5.0%） in low exposure to MPA group,31 cases（51.7%） in target exposure to MPA group and 26 cases（43.3%） in high exposure to MPA group.The mean doses of CsA in low exposure to MPA group,target exposure to MPA group and high exposure to MPA group were（166.67±14.43） mg/d,（137.10±41.27） mg/d and（128.85±37.88） mg/d respectively,exhibiting a decreasing tendency,while there was no significant difference among groups（P〉0.05）.Conclusion Under the condition of MMF dose adjustment based on clinical events without MPA AUC monitoring,MPA tends to be highly exposed in renal allograft recipients.There are significant inter-individual variations in MPA pharmacokinetics,and it is necessary to perform MMF monitoring in treatment for renal allograft recipients.