CAJ | 학술논문

目的采用USC*PACK软件建立中国癫(癎)儿童拉莫三嗪的群体药代动力学(PPK)模型,促进个体化用药.方法回顾性收集60例癫(癎)患儿应用拉莫三嗪(LTG)的临床数据,并根据联合用药情况,将114个血药浓度点分成LTG+丙戊酸(VPA)组(n=56)、LTG+肝药酶诱导剂(EI)组(n=26)、LTG+EI+VPA组(n=16)及单用LTG组(n=16).血药浓度均为临床常规监测的稳态浓度.应用USC*PACK软件中的非参数最大期望程序(NPEM Program),推算最优的PPK参数值,并建立模型.应用此模型和USC*PACK软件中的贝叶斯拟合程序(Bayesian fitting program),对患儿的血药浓度进行预测;求算平均预测误差(MPE),预测误差均方(MSPE)判断预测的准确度和精密度,验证PPK模型.结果最大似然值为-192.87,LTG的最佳PPK参数值为:Ka=(1.97±1.66)h~(-1);Vs=(1.07±0.89)L/kg;Kel=(0.05 ±0.05)h~(-1).血药浓度拟合值与观测值的相关系数r=0.99,回归方程为Y_(OBS)=-0.09+1.05×Y_(PRED)(R~2=0.98,P<0.001).MPE为-0.16 μg/mL,MSPE为0.28(μg/mL)~2.结论在USC*PACK软件中,应用自行建立的PPK模型和Bayes法,估算个体PK参数,再进一步算出半衰期、峰谷浓度以及调药后的峰谷浓度,甚至可以模拟出调药前后的药时曲线,满足临床上的多种需求,使得临床用药从传统的经验用药模式提高到科学的个体化用药模式.
목적 채용USC*PACK연건건립중국전(간)인동랍막삼진적군체약대동역학(PPK)모형,촉진개체화용약.방법 회고성수집60례전(간)환인응용랍막삼진(LTG)적림상수거,병근거연합용약정황,장114개혈약농도점분성LTG+병무산(VPA)조(n=56)、LTG+간약매유도제(EI)조(n=26)、LTG+EI+VPA조(n=16)급단용LTG조(n=16).혈약농도균위림상상규감측적은태농도.응용USC*PACK연건중적비삼수최대기망정서(NPEM Program),추산최우적PPK삼수치,병건립모형.응용차모형화USC*PACK연건중적패협사의합정서(Bayesian fitting program),대환인적혈약농도진행예측;구산평균예측오차(MPE),예측오차균방(MSPE)판단예측적준학도화정밀도,험증PPK모형.결과 최대사연치위-192.87,LTG적최가PPK삼수치위:Ka=(1.97±1.66)h~(-1);Vs=(1.07±0.89)L/kg;Kel=(0.05 ±0.05)h~(-1).혈약농도의합치여관측치적상관계수r=0.99,회귀방정위Y_(OBS)=-0.09+1.05×Y_(PRED)(R~2=0.98,P<0.001).MPE위-0.16 μg/mL,MSPE위0.28(μg/mL)~2.결론 재USC*PACK연건중,응용자행건립적PPK모형화Bayes법,고산개체PK삼수,재진일보산출반쇠기、봉곡농도이급조약후적봉곡농도,심지가이모의출조약전후적약시곡선,만족림상상적다충수구,사득림상용약종전통적경험용약모식제고도과학적개체화용약모식.
Objective To establish the population pharmacokinetics(PPK)model of Lamotrigine(LTG)in children with epilepsy in China for promoting individualized dosage regimen. Methods The sparse data of LTG serum concentrations from 60 pediatric patients with epilepsy were collected. One hundred and fourteen serum concentration points were divided into LTG+valproic acid (VPA) group(n=56),LTG+enzymatic inducer(E1)group(n=26),LTG+EI+VPA group(n=16)and single LTG group(n=16).The serum drug concentrations were the clinical routinely tested steadv state concentrations.The LTG PPK parameters were calculated using the non-parametric expectation maximization(NPEM) Program of USC*PACK software,and then a PPK model was established. Based on this model,LTG serum concentrations were predicted with Bayesian fitting program of USC*PACK software.Mean prediction error(MPE)and mean squared prediction error(MSPE) were calculated to evaluate the accuracy and precision of the concentration prediction and to valid the PPK model.Results The greatest likelihood was-192.87.Optimum PPK parameters were:Ka=(1.97 1.66)h~(-1);Vs=(1.07±0.89)L/kg;Kel=(0.05±0.05)h~(-1).The linear regression function Y_(OBS)=-0.09+1.05 Y_(PRED)(R~2=0.98,P<0.001),and determination of coefficient was 0.98.MPE was-0.16 g/mL,and MSPE was 0.28(μg/mL)~2.Conclusion A PPK model of LTG in children with epilepsy in China can be successfully established using the USC*PACK software, based on which LTG serum concentrations can be predicted accurately with a Bayesian approach.