本文選題：兒童 + 甲氨蝶呤��； 參考：《中國(guó)新藥與臨床雜志》2017年02期

【摘要】：目的建立兒童甲氨蝶呤(MTX)群體藥動(dòng)學(xué)(PPK)模型,考察聯(lián)合用藥對(duì)其藥動(dòng)學(xué)的影響。方法收集294例急性淋巴細(xì)胞白血病(ALL)患兒行大劑量MTX化療后的血藥濃度數(shù)據(jù)和臨床資料。將患兒隨機(jī)分為兩組,模型組(n=245)采用NLME程序進(jìn)行PPK分析,建立二房室藥動(dòng)學(xué)模型,考察各協(xié)變量對(duì)參數(shù)CL_1、CL_2、V_1和V_2的影響。用擬合優(yōu)度、自舉法和正態(tài)化預(yù)測(cè)分布誤差對(duì)最終模型的性能進(jìn)行內(nèi)部驗(yàn)證。采用驗(yàn)證組患兒(n=49)的數(shù)據(jù)計(jì)算平均預(yù)測(cè)誤差(MPE)、平均絕對(duì)預(yù)測(cè)誤差(MAE)、平均預(yù)測(cè)誤差平方(MSE)、平方預(yù)測(cè)誤差(SPE)和均方根預(yù)測(cè)誤差(RMSE)對(duì)模型進(jìn)行外部驗(yàn)證。結(jié)果最終模型藥動(dòng)學(xué)參數(shù)的群體典型值為:V_1=20.51 L·m~(-2),V_2=2.95 L·m~(-2),CL_1=6.81 L·m~(-2)·h~(-1),CL_2=0.17 L·m~(-2)·h~(-1)。質(zhì)子泵抑制劑(PPIs)、青霉素類藥物、非甾體抗炎藥(NSAIDs)分別使MTX清除率下降20.5%、19.7%、13.1%。其他協(xié)變量與MTX清除率無(wú)顯著相關(guān)性。最終模型的預(yù)測(cè)性能較好且優(yōu)于基本模型。單用MTX患兒體內(nèi)MTX清除率高于合用PPIs、青霉素類藥物、NSAIDs患兒體內(nèi)MTX清除率(P0.05)。結(jié)論本研究成功建立了ALL患兒MTX化療后的PPK模型,模型結(jié)構(gòu)表明合用PPIs、青霉素類藥物、NSAIDs可使MTX的清除率降低。
[Abstract]:Objective to establish a population pharmacokinetic model of MTX in children and to investigate the effect of combined drug therapy on its pharmacokinetics. Methods Blood drug concentration data and clinical data were collected from 294 children with acute lymphoblastic leukemia (ALL) after high dose MTX chemotherapy. The children were randomly divided into two groups. The model group was analyzed by PPK with NLME program, and the two-chamber pharmacokinetic model was established. The performance of the final model is verified by the goodness of fit, bootstrap method and normal prediction distribution error. The model was verified by using the data of the validation group, such as the mean prediction error (MPEGE), the mean absolute prediction error (mae), the mean prediction error squared (MSE), the square prediction error (SPE) and the root-mean-square prediction error (RMSE). Results the typical population value of pharmacokinetic parameters of the final model was as follows: 1 / V _ 1: 20. 51 L / m ~ (-2) / V _ (2) ~ (2) ~ (95) L ~ (2) L ~ (-1) / L ~ (-1) / L ~ (-1) / L ~ (-1) / L ~ (-1) / L ~ (-1) / L ~ (-1) / L / L / L / L / L / L / L / L / L / L / L / L / L / L / L / L / L Proton pump inhibitor PPP Isa penicillin and NSAIDs reduced the clearance rate of MTX by 20.5 and 19.713.1 respectively. There was no significant correlation between other covariables and MTX clearance. The prediction performance of the final model is better than that of the basic model. The clearance rate of MTX in children with MTX alone was higher than that in children with MTX. The clearance rate of MTX in children with penicillin drugs was higher than that in children with P0. 05%. Conclusion the model of PPK after MTX chemotherapy in children with ALL was successfully established. The structure of the model showed that the clearance rate of MTX could be decreased by penicillin drugs combined with MTX.
【作者單位】： 武漢市兒童醫(yī)院藥學(xué)部;
【基金】：湖北省衛(wèi)生廳2011-2012年度科研項(xiàng)目(JX5B74)
【分類號(hào)】：R969.1

【參考文獻(xiàn)】

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1 魏盈盈;焦n，

本文編號(hào)：1969164