丙戊酸致癲癇患者血氨升高的群體藥效學(xué)分析
發(fā)布時(shí)間：2018-07-14 08:55
【摘要】：目的:建立群體藥效學(xué)(PPD)模型考察丙戊酸(VPA)致癲癇患者血氨升高的量-效關(guān)系,以促進(jìn)安全用藥。方法:搜索提取已發(fā)表的研究資料,以患者VPA血漿藥物濃度作為藥動(dòng)學(xué)指標(biāo),血氨濃度作為藥效學(xué)指標(biāo),采用非線性混合效應(yīng)建模進(jìn)行數(shù)據(jù)分析。藥效學(xué)結(jié)構(gòu)模型選用Sigmoid-Emax模型。用擬合優(yōu)度、自舉法和直觀預(yù)測(cè)檢驗(yàn)對(duì)模型的預(yù)測(cè)性能進(jìn)行內(nèi)部驗(yàn)證。用未參與建模的數(shù)據(jù)對(duì)模型進(jìn)行外部驗(yàn)證。結(jié)果:PPD模型參數(shù)的群體典型值分別為:E0(基線效應(yīng)值)=25.09μg·dL~(-1),EC50(達(dá)最大效應(yīng)一半時(shí)效應(yīng)室濃度)=107.26 mg·L~(-1),γ(陡度因子)=4.00,Emax(最大效應(yīng)參數(shù))=471.95μg·dL~(-1)。內(nèi)部驗(yàn)證和外部驗(yàn)證結(jié)果表明最終模型穩(wěn)定,預(yù)測(cè)結(jié)果可靠。結(jié)論:本研究成功建立了能夠反映患者丙戊酸血藥濃度與血氨水平之間定量關(guān)系的PPD模型,可為臨床安全用藥提供參考。
[Abstract]:Aim: to establish a population pharmacodynamics (PPD) model to investigate the dose-effect relationship of elevated blood ammonia in patients with epilepsy induced by valproic acid (VPA) in order to promote safe drug use. Methods: the published data were searched and extracted. The plasma concentration of VPA was used as the pharmacokinetic index and the concentration of blood ammonia as the pharmacodynamics index. The data were analyzed by nonlinear mixed effect modeling. Sigmoid-Emax model was used for pharmacodynamics structure model. The predication performance of the model is verified by the goodness of fit, bootstrap method and visual prediction test. External validation of the model with non-participating modeling data. Results the typical population values of the weight PPD model parameters were: 1: E0 (baseline effect value) 25.09 渭 g dL-1) EC50 (maximum effect half time) 107.26 mg L-1, 緯 (steepness factor) 4.00 渭 g dLmax (maximum effect parameter) 471.95 渭 g dL ~ (-1). The results of internal and external verification show that the final model is stable and the prediction results are reliable. Conclusion: this study successfully established a PPD model which can reflect the quantitative relationship between serum valproic acid concentration and blood ammonia level in patients with valproic acid.
【作者單位】： 武漢市婦女兒童醫(yī)療保健中心;武鋼第二職工醫(yī)院;
【基金】：2016年度武漢市衛(wèi)生計(jì)生科研基金資助項(xiàng)目(編號(hào):WX16B18)
【分類號(hào)】：R742.1
，
本文編號(hào)：2121131
[Abstract]:Aim: to establish a population pharmacodynamics (PPD) model to investigate the dose-effect relationship of elevated blood ammonia in patients with epilepsy induced by valproic acid (VPA) in order to promote safe drug use. Methods: the published data were searched and extracted. The plasma concentration of VPA was used as the pharmacokinetic index and the concentration of blood ammonia as the pharmacodynamics index. The data were analyzed by nonlinear mixed effect modeling. Sigmoid-Emax model was used for pharmacodynamics structure model. The predication performance of the model is verified by the goodness of fit, bootstrap method and visual prediction test. External validation of the model with non-participating modeling data. Results the typical population values of the weight PPD model parameters were: 1: E0 (baseline effect value) 25.09 渭 g dL-1) EC50 (maximum effect half time) 107.26 mg L-1, 緯 (steepness factor) 4.00 渭 g dLmax (maximum effect parameter) 471.95 渭 g dL ~ (-1). The results of internal and external verification show that the final model is stable and the prediction results are reliable. Conclusion: this study successfully established a PPD model which can reflect the quantitative relationship between serum valproic acid concentration and blood ammonia level in patients with valproic acid.
【作者單位】： 武漢市婦女兒童醫(yī)療保健中心;武鋼第二職工醫(yī)院;
【基金】：2016年度武漢市衛(wèi)生計(jì)生科研基金資助項(xiàng)目(編號(hào):WX16B18)
【分類號(hào)】：R742.1
，
本文編號(hào)：2121131
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