【摘要】 目的构建茶碱的早产儿生理药代动力学（PBPK）模型,并进行药代动力学（PK）行为预测。方法通过文献收集茶碱的理化性质参数和临床试验数据,用Gastro Plus软件搭建PBPK模型,验证在不同人群的准确性及适用性,并用于预测早产儿人群,通过参数优化预测茶碱在早产儿个体的PK行为。结果经验证模型有良好的准确性和适用性,药物浓度-时间曲线下面积AUC_预测/AUC_观测比值在0.85¹.15,且决定系数（R²）>0.85,观测值与预测曲线的重合度良好,误差较小。结论用Gastro Plus构建的茶碱早产儿PBPK模型能够较好地模拟药物在体内的PK过程,为个体化给药提供参考;同时,补充中国早产儿和婴幼儿PBPK建模的重要生理和解剖学数据,可以提高模拟的准确性。更多还原

【Abstract】 Objective To establish a physiologically based pharmacokinetic( PBPK) model and predict the pharmacokinetics( PK) of theophylline in premature infants. Methods Collected the drug-specific properties and clinical trial data of theophylline from published literatures,theophylline PBPK model was established by Gastro Plus simulation technology. The accuracy and applicability of model were verified in different type populations. It was also verified to predict premature population. The model was used to predict the PK of theophylline in each preterm after parameter optimization. Results It was verified with good accuracy and applicability. The area under curve AUCsim/AUCobsratio was0. 85-1. 15 and the coefficient of determination( R~2) was greater than0. 85. It’s less errors and good fit of the simulated value and observed data in each preterm. Conclusion The PBPK model of theophylline established by Gastro Plus can reflect the PK process of theophylline in premature infants and provide a reference for theophylline individualized medication. It will be able to improve the model accuracy by the supplement of the important physiological and anatomical data of premature and infants in China.更多还原