發(fā)布時(shí)間：2018-11-12 09:14

【摘要】：目的:建立國(guó)人紫杉醇(paclitaxel,PTX)群體藥動(dòng)學(xué)(population pharmacokinetic,PPK)模型,為制定個(gè)體化給藥方案提供理論支持。方法:收集138例接受紫杉醇治療的腫瘤患者(建模組105例,驗(yàn)證組33例)210個(gè)血樣,HPLC法測(cè)定紫杉醇血藥濃度,PCR-RFLP法檢測(cè)MDR1 C3435T。應(yīng)用非線性混合效應(yīng)模型(NONMEM)法,考察MDR1 C3435T基因多態(tài)性、合并用藥及病理生理因素對(duì)紫杉醇藥動(dòng)學(xué)參數(shù)的影響,建立紫杉醇PPK模型。對(duì)模型進(jìn)行擬合優(yōu)度診斷、自舉法(Bootstrap)內(nèi)部驗(yàn)證,正態(tài)預(yù)測(cè)分布誤差法(NPDE)及外部驗(yàn)證考察模型預(yù)測(cè)能力。結(jié)果:紫杉醇清除率(CL)和表觀分布容積(Vd)的群體典型值分別為64.7 L·h~(-1)和1 240 L,患者內(nèi)生肌酐清除率(CLcr)和給藥速率(RATE)顯著影響紫杉醇清除率。最終模型Bootstrap法驗(yàn)證結(jié)果與模型計(jì)算值相符,擬合優(yōu)度、準(zhǔn)確度及精密度均優(yōu)于最簡(jiǎn)模型。結(jié)論:紫杉醇PPK最終模型穩(wěn)定、有效,可結(jié)合Bayesian反饋法為臨床優(yōu)化給藥方案提供科學(xué)依據(jù)。
[Abstract]:Aim: to establish a Chinese paclitaxel (paclitaxel,PTX) population pharmacokinetics (population pharmacokinetic,PPK) model to provide theoretical support for the formulation of individualized regimen. Methods: a total of 210 blood samples were collected from 138 patients with tumor treated with paclitaxel (105 patients in model group and 33 patients in validation group). The concentration of paclitaxel was measured by HPLC and MDR1 C3435T by PCR-RFLP. The effects of MDR1 C3435T gene polymorphism, combined drug use and pathophysiological factors on the pharmacokinetic parameters of paclitaxel were investigated by nonlinear mixed effect model (NONMEM). The paclitaxel PPK model was established. The goodness of fit diagnosis, bootstrap (Bootstrap) internal verification, normal prediction distribution error method (NPDE) and external validation are used to evaluate the model prediction ability. Results: the population typical values of paclitaxel clearance rate (CL) and apparent distributed volume (Vd) were 64.7 L h ~ (-1) and 1 240 L, respectively. Endogenous creatinine clearance (CLcr) and administration rate (RATE) significantly affected taxol clearance. The result of the final model Bootstrap method is in agreement with the calculated value of the model, and the goodness of fit, accuracy and precision are better than the simplest model. Conclusion: the final model of paclitaxel PPK is stable and effective. It can provide scientific basis for clinical optimization of drug delivery regimen combined with Bayesian feedback method.
【作者單位】： 福建醫(yī)科大學(xué)附屬第一醫(yī)院;廈門市婦幼保健院藥學(xué)部;
【基金】：福建省衛(wèi)生系統(tǒng)中青年骨干人才培養(yǎng)計(jì)劃重點(diǎn)項(xiàng)目(編號(hào):2014-ZQN-ZD-15) 教育部留學(xué)回國(guó)人員第46批科研啟動(dòng)基金(編號(hào):2013B019)
【分類號(hào)】：R969.1

【相似文獻(xiàn)】

相關(guān)期刊論文 前4條

1 芮建中，儲(chǔ)小曼，潘浩，，陳剛;NONMEM法估算癲癇患者游離苯妥英的群體藥物動(dòng)力學(xué)參數(shù)[J];中國(guó)藥學(xué)雜志;1995年09期

2 張興安,芮建中,吳群林,施沖,王若松;NONMEM法分析靜滴異丙酚在中國(guó)人體的群體藥代動(dòng)力學(xué)[J];中國(guó)臨床藥理學(xué)雜志;2004年06期

3 白玉國(guó);張愛琴;劉翎;趙強(qiáng);趙秀麗;;用NONMEM法建立中國(guó)成年患者服用地高辛群體藥動(dòng)學(xué)模型[J];中國(guó)藥學(xué)雜志;2009年18期

4 焦正,鐘明康,施孝金,胡敏,李中東,王大猷,張莉莉,張靜華,王宏圖;NONMEM法考察中國(guó)癲癇患者丙戊酸和卡馬西平的藥動(dòng)學(xué)相互作用[J];中國(guó)藥學(xué)雜志;2004年02期

本文編號(hào)：2326691