The accuracy of physiologically based pharmacokinetic (PBPK) model prediction in children, especially those younger than 2 years old, has not been systematically evaluated. The aim of this study was to characterize the pediatric predictive performance of the PBPK approach for 10 drugs extensively metabolized by CYP1A2 (theophylline), CYP2C8 (desloratidine, montelukast), CYP2C9 (diclofenac), CYP2C19 (esomeprazole, lansoprazole), CYP2D6 (tramadol), and CYP3A4 (itraconazole, ondansetron, sufentanil). Model performance in children was evaluated by comparing simulated plasma concentration–time profiles with observed clinical results for each drug and age group. PBPK models reasonably predicted the pharmacokinetics of desloratadine, diclofenac, itraconazole, lansoprazole, montelukast, ondansetron, sufentanil, theophylline, and tramadol across all age groups. Collectively, 58 out of 67 predictions were within 2‐fold and 43 out of 67 predictions within 1.5‐fold of observed values. Developed PBPK models can reasonably predict exposure in children age 1 month and older for an array of predominantly CYP metabolized drugs.

中文翻译：

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儿童主要细胞色素P450广泛代谢的药物的基于生理的药代动力学（PBPK）建模的预测性能

尚未系统评估儿童，尤其是2岁以下儿童的生理基础药代动力学（PBPK）模型预测的准确性。这项研究的目的是表征PBPK方法对10种被CYP1A2（茶碱），CYP2C8（去氯雷替丁，孟鲁司特），CYP2C9（双氯芬酸），CYP2C19（依美拉唑，兰索拉唑），trasoDolD（6）广泛代谢的药物的儿科预测性能，CYP3A4（伊曲康唑，恩丹西酮，舒芬太尼）。通过将模拟的血浆浓度-时间曲线与每种药物和年龄组的观察到的临床结果进行比较，评估了儿童的模型表现。PBPK模型可以合理地预测地氯雷他定，双氯芬酸，伊曲康唑，兰索拉唑，孟鲁司特，恩丹西酮，舒芬太尼，茶碱的药代动力学，和所有年龄段的曲马多。总体而言，67个预测中的58个在2倍以内，而67个预测中的43个在观测值的1.5倍以内。开发的PBPK模型可以合理地预测1个月及以上儿童的一系列主要CYP代谢药物的暴露情况。