Developmental changes in children can affect the disposition and clinical effects of a drug, indicating that scaling an adult dose simply down per linear weight can potentially lead to overdosing, especially in very young children. Physiologically-based pharmacokinetic (PBPK) models are compartmental, mathematical models that can be used to predict plasma drug concentrations in pediatric populations and acquire insight into the influence of age-dependent physiological differences on drug disposition. Pediatric PBPK models have generated attention in the last decade, because physiological parameters for model building are increasingly available and regulatory guidelines demand pediatric studies during drug development. Due to efforts from academia, PBPK model developers, pharmaceutical companies and regulatory authorities, examples are now available where clinical studies in children have been replaced or informed by PBPK models. However, the number of pediatric PBPK models and their predictive performance still lags behind that of adult models. In this review we discuss the general pediatric PBPK model principles, indicate the challenges that can arise when developing models, and highlight new applications, to give an overview of the current status and future perspective of pediatric PBPK modeling.

儿童的发育变化会影响药物的配置和临床效果，这表明仅将线性剂量的成人剂量降低会潜在地导致用药过量，尤其是在年幼的儿童中。基于生理的药代动力学（PBPK）模型是可用于预测儿科人群血浆药物浓度并获得对年龄依赖性生理差异对药物处置影响的洞察力的部分数学模型。在过去的十年中，儿科PBPK模型引起了人们的关注，因为用于模型构建的生理参数越来越多，并且法规指南要求在药物开发过程中进行儿科研究。由于学术界，PBPK模型开发人员，制药公司和监管机构的努力，现在可以用PBPK模型替代或告知儿童临床研究的例子。然而，儿科PBPK模型的数量及其预测性能仍落后于成人模型。在这篇综述中，我们讨论了小儿PBPK模型的一般原理，指出了在开发模型时可能出现的挑战，并着重介绍了新的应用，以概述小儿PBPK模型的当前状态和未来前景。