有限采样法用于肾移植受者霉酚酸酯血药浓度监测的分析

Use of limited sampling strategy to analyse MMF blood concentration in renal transplant recipients

目的观察肾移植受者采用霉酚酸酯（mycophenolate mofetil,MMF）进行免疫抑制的临床应用及其血药浓度监测情况,为临床合理用药提供参考。方法采用回顾性分析方法,收集2012年8月-2015年12月在四川省人民医院移植中心接受同种异体肾移植术并服用MMF患者23例,所有患者均采用三联免疫抑制方案他克莫司（tacrolimus,FK506）＋MMF＋泼尼松（prednisone,PRED）治疗,并于2015年5月-2016年4月进行霉酚酸（mycophenolic acid,MPA）监测;根据口服MMF剂量,将患者分为MMF剂量组A（MMF=0.25 g/12 h,n=2）,MMF剂量组B（MMF=0.5 g/12h,n=11）,MMF剂量组C（MMF=0.75 g/12h,n=10）。本试验采用有限采样法（C0,C0.5 h,C2 h）估算MPA AUC暴露值,根据MPA AUC暴露值,将患者分为MPA低暴露组（〈30μg·h/m L）,MPA目标暴露组（30-60μg·h/m L）,MPA高暴露组（〉60μg·h/m L）;并分析3组暴露组患者的基本资料、MMF用量、合并用药、肝肾功能等指标。结果 23例患者的平均体质量为（54.58±16.22）kg,血肌酐浓度平均为（172.73±166.84）mol/L,肾小球滤过率平均为（67.72±38.2）m L/min,MPA低暴露组1例（4.3%）,MPA目标暴露组14例（60.9%）,MPA高暴露组8例（34.7%）;对目标暴露组和高暴露组进行独立样本t检验,发现目标组和高暴露组间他克莫司（tacrolimus,FK506）、MMF和泼尼松（prednisone,PRED）间用量并无显著性差异;对3组数据进行非参数检验,发现3组间肝肾功主要指标间是无显著差异。结论服用MMF进行免疫抑制的肾移植受者间具有较大的个体差异,因此应对其进行治疗药物监测,根据MPA AUC值进行剂量的调整,达到更好的免疫抑制状态。

Objective To investigate the renal transplant recipients using mycophenolate mofetil（MMF） in clinical immune therapy and the data of plasma concentration,and provide the reference for rational drug use in clinical application. Methods By retrospective survey method,the 23 renal transplantation patients data were collected who were taken kidney transplant in the multi-organ transplant center of Sichuan provincial people＇s hospital from August 2012 to December 2015. All patients were treated with triple immunosuppressive regimen（FK506 ＋ MMF ＋ PRED）,and were monitoring the MPA plasma concentration from May 2015 to April 2016. According to oral dose of MMF,the patients were divided into group A（MMF = 0. 25 g/12 h,n= 2）,group B（MMF = 0. 5 g/12 h,n = 11）,group C（MMF = 0. 75 g/12 h,n = 10）. This test used limited sampling strategy（C0,C0. 5 h,C2 h） to estimate MPA AUC exposure value. According to MPA AUC exposure value,the patients were divided into MPA low exposure group（ 30 μg · h/mL）,MPA target exposure group（30-60 μg·h/mL）,MPA high exposure group（ 〉60 μg·h/mL）. And the basic information,MMF dosage,drug combinations,liver and kidney function indicators etc were analyzed. Results The average body mass of 23 patients was（54. 58 ± 16. 22） kg,mean serum creatinine concentration was（172. 73 ± 166. 84） mol/L,the average glomerular filtration rate was（67. 72 ± 38. 2） mL/min,MPA low exposure group was one case（4. 3%）,MPA target exposure group was 14 cases（60. 9%）,MPA high exposure group was 8 cases（34. 7%）. The target exposure group and the high exposure group were applied independent samples t-test,found that between the target exposure group and high exposure group,the dosage of FK506,MMF and PRED were no statistical differences. The liver and kidney function indicators of three groups were applied Kruskal-Wallis test,found that the three groups were no statistical differences. Conclusion Applied MMF among kidney transplant recipients have greater individual differences,and therefore should carry out therapeutic drug monitoring to achieve better immunosuppression and adjust dose according to MPA AUC value.