肾移植受者早期霉酚酸暴露量估算模型研究  

Estimation model for the exposure of mycophenolic acid in early renal transplant recipients

作　　者：张寒娟[1] 丁建强[2] 韩文超 陈永妍[1] 王高彪 丁蕊 袁冬冬[1] ZHANG Hanjuan;DING Jianqiang;HAN Wenchao;CHEN Yongyan;WANG Gaobiao;DING Rui;YUAN Dongdong(Dept.of Pharmacy,Zhengzhou No.7 People’s Hospital,Zhengzhou 450016,China;Dept.ofPharmacy,Henan General Hospital of Armed Police,Zhengzhou 450052,China)

机构地区：[1]郑州市第七人民医院药学部,郑州450016 [2]武警河南总队医院药学部,郑州450052

出　　处：《中国药房》2023年第20期2530-2534,共5页China Pharmacy

基　　金：河南省医学科技攻关计划联合共建项目(No.LHGJ20200732)。

摘　　要：目的建立肾移植早期受者体内霉酚酸(MPA)暴露量[以12 h内血药浓度-时间曲线下面积(AUC0-12 h)计]的估算模型。方法选择20例接受吗替麦考酚酯(MMF)+他克莫司+甲泼尼龙三联免疫抑制治疗的肾移植受者,分别于术后第15天口服吗替麦考酚酯分散片(750 mg,q12 h)前及服药后0.5、1.0、1.5、2.0、3.0、4.0、6.0、8.0、12.0 h采集血样,测定MPA血药浓度,计算MPA的药动学参数;采用多元线性逐步回归分析法,拟合估算受者人群体内MPA-AUC0-12 h的有限采样法简化计算公式,并采用BlandAltman方法评价该公式与经典药动学方法之间的一致性。结果20例受者MPA的给药前血药浓度(c_(0))为(1.53±0.84)μg/mL,药峰浓度(c_(max))为(12.07±5.97)μg/mL,半衰期(t_(1/2))为(5.41±3.67)h,药峰时间(t_(max))为(1.58±0.75)h,f AUC_(0-12 h)(按经典药动学方法计算出的AUC_(0-12 h))为(33.95±13.40)μg·h/mL。使用“4.0、8.0、12.0 h”三点采样估算MPA-AUC_(0-12 h)的简化计算公式为AUC_(0-12 h)=12.058+2.819c_(4.0)+7.045c_(8.0)+3.879c_(12.0)(R^(2)=0.934),预测值与fAUC_(0-12 h)有很好的相关性及一致性,95.0%的预测值在x±1.96SD(标准差)范围内。结论成功建立了肾移植受者早期MPA暴露量估算模型,且该模型有较好的预测精度,并具有采样点少的优势。OBJECTIVE To establish the estimation model for the exposure of mycophenolic acid(MPA)in early renal transplant recipients[calculated by the area under the plasma concentration-time curve with 12 h(AUC_(0-12 h))].METHODS Twenty kidney transplant recipients,who received triple immunosuppressive therapy of mycophenolate mofetil(MMF)+tacrolimus+methylprednisolone,were selected and given MMF dispersible tablets(750 mg,q12 h)on the 15th day after the operation;the blood samples were collected from the patients before and 0.5,1.0,1.5,2.0,3.0,4.0,6.0,8.0,12.0 hours after the administration,respectively.The blood concentration of MPA was determined,and the pharmacokinetic parameters of MPA were calculated.The multivariate linear stepwise regression analysis method was used to fit an estimation formula for the finite sampling method suitable for MPA-AUC_(0-12 h) of the recipients.Bland-Altman analysis was used to evaluate the agreement between the estimation formula and the classical pharmacokinetic method.RESULTS The main pharmacokinetic parameters of MPA in 20 renal transplant recipients:c_(0) was(1.53±0.84)μg/mL,c_(max) was(12.07±5.97)μg/mL,t_(1/2) was(5.41±3.67)h,t_(max) was(1.58±0.75)h,and the average AUC_(0-12 h) calculated by the classical pharmacokinetic method was(33.95±13.40)μg·h/mL.MPA-AUC_(0-12 h) was estimated with sampling points of“4.0,8.0,12.0 h”;the simplified calculation formula was AUC_(0-12 h)=12.058+2.819c_(4.0)+7.045c_(8.0)+3.879c_(12.0)(R^(2)=0.934).The predicted value had a good correlation and consistency with the measured value,and 95.0%of predicted values did not exceed the x±1.96SD(standard deviation)range.CONCLUSIONS The estimation model is established successfully for the exposure of MPA in early renal transplant recipients;the model has better prediction accuracy and fewer sampling points.

关 键 词：霉酚酸 暴露量 肾移植 药动学 有限采样法 预测模型 

分 类 号：R969[医药卫生—药理学]