有限取样法研究吗替麦考酚酯的药时曲线下面积及其验证  

Study of area under drug time curve of mycophenol ester by finite sampling method and its verification

作　　者：陈仕蕾 蔡文娥 孙煦勇 梁园 CHEN Shilei;CAI Wen′e;SUN Xuyong;LIANG Yuan(Guilin Medical College,Guangxi Zhuang Autonomous Region,Guilin 541199,China;不详)

机构地区：[1]桂林医学院,广西壮族自治区桂林市541199 [2]中国人民解放军联勤保障部队第九二三医院药剂科,南宁市530021 [3]中国人民解放军联勤保障部队第九二三医院器官移植中心暨广西移植医学重点实验室/广西移植医学工程技术研究中心,南宁市530021 [4]广西医科大学第二附属医院移植医学中心/广西器官捐献与移植研究重点实验室,南宁市530007

出　　处：《临床合理用药杂志》2023年第10期21-26,共6页Chinese Journal of Clinical Rational Drug Use

基　　金：广西自然科学基金(2015GXNSFAA139163);国家自然科学基金面上项目(81670596)。

摘　　要：目的采用酶放大免疫法检测肾移植术后早期中国成年受者的吗替麦考酚酸(MPA)药代动力学特点,应用有限取样法确定血MPA浓度—时间曲线下面积(MPA AUC)的拟合方程,并进行临床验证。方法将纳入研究的52名受者依据硬币投掷方法随机分为研究组和验证组,所有受者均采用吗替麦考酚酯(MMF)+他克莫司(Tac)、泼尼松(Pred)三联免疫抑制方案。于术后第7天采集2组受者服药前(0 h)、服药后0.5、1、1.5、2、4、6、8、10、12 h(C_(0h)、C_(0.5h)、C_(1h)、C_(1.5h)、C_(2h)、C_(4h)、C_(6h)、C_(8h)、C_(10h)、C_(12h))的血液样本,使用非房室模型分析确定药代动力学参数,在研究组中通过多元线性回归分析确定预测MPA AUC_(0-12h)的有限取样拟合方程,在验证组中评估拟合方程的一致性。结果研究组:3点拟合方程为:MPA AUC_(0-12h)=-1.457+6.853C_(8h)+2.448C_(2h)+2.134C_(4h)(R^(2)=0.965,P<0.001);4点拟合方程为:MPA AUC_(0-12h)=-2.39+7.108C_(8h)+1.928C_(2h)+1.973C_(4h)+0.765C_(1.5h)(R^(2)=0.982,P<0.001)。验证组:3点方程:R^(2)=0.98,95%置信区(-9.1,6.5),有0/21(0%)的受者在95%置信区外,MAE%=2.00%,MPE%=5.49%;4点方程:R^(2)=0.99,95%置信区(-7.0,6.4),有0/21(0%)的受者在95%置信区外,MAE%=0.76%,MPE%=5.25%。结论肾移植受者术后第7天选取合适的取样点,可得到相对精确MPA AUC_(0-12h)的拟合方程,使肾移植受者术后早期MPA的血药浓度监测方案更经济、快捷,给临床医师及时调整治疗策略提供参考。Objective To assess the pharmaeokinetics of mycophenolate acid(MPA)in Chinese adult recipients early after renal transplantation by an enzyme multiplied immunoassay technique and to establish a limited sampling strategy to predict the area under the concentration time curve of blood 1evels of mycophenolic acid(MPA AUC).Methods The 52 recipients included in the study were randomly divided into modeling group and validation group according to coin throwing method.All recipients received a triple immunosuppressive regimen of mortemycophenol ester(MMF)+tacrolimus(Tac)and prednisone(Pred).On the 7th day after the renal transplantation,blood samples were collected at 0 h(pre-dose)and at 0.5,1,1.5,2,4,6,8,10 and 12 h post-dose(C_(0h),C_(0.5h),C_(1h),C_(1.5h),C_(2h),C_(4h),C_(6h),C_(8h),C_(10h),C_(12h),respectively),Non-atrioventricular model was used to determine the data obtained from individual patients.The estimated AUC was calculated with these 3 or 4 points of MPA concentrations with ultiple stepwise regression analysis in modeling group.The consistency evaluation of different models were evaluated in the validation group.Results Modeling group:The 3 point equation was:MPA AUC_(0-12h)=-1.457+6.853C_(8h)+2.448C_(2h)+2.134C_(4h)(R^(2)=0.965,P<0.001);the 4 point equation was:MPA AUC_(0-12h)=-2.39+7.108C_(8h)+1.928C_(2h)+1.973C_(4h)+0.765C_(1.5h)(R^(2)=0.982,P<0.001).Validation group:The 3 point equation:R^(2)=0.98,95%confidence intervals was(-9.1,6.5),0/21(0%)of patients were outside the 95%confidence interval,MAE%=2.00%,MPE%=5.49%;the 4 point equation:R^(2)=0.99,95%confidence intervals was(-7.0,6.4),0/21(0%)of patients were outside the 95%confidence interval,MAE%=0.76%,MPE%=5.25%.Conclusion In adults recipents 7th day after renal transplantation,different point equation can be chosen to predict MPA AUC_(0-12h) accurately,which makes the limited sampling strategy more convenient,economic,providing reference for clinicians to adjust treatment strategies in time.

关 键 词：吗替麦考酚酯 肾移植 有限取样法 临床验证 

分 类 号：R969.1[医药卫生—药理学]