Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
Department of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.
J Pharm Pharmacol. 2019 Apr;71(4):603-642. doi: 10.1111/jphp.12955. Epub 2018 Jul 3.
In this review, the current biopharmaceutical approaches for evaluation of oral formulation performance in paediatrics are discussed.
The paediatric gastrointestinal (GI) tract undergoes numerous morphological and physiological changes throughout its development and growth. Some physiological parameters are yet to be investigated, limiting the use of the existing in vitro biopharmaceutical tools to predict the in vivo performance of paediatric formulations. Meals and frequencies of their administration evolve during childhood and affect oral drug absorption. Furthermore, the establishment of a paediatric Biopharmaceutics Classification System (pBCS), based on the adult Biopharmaceutics Classification System (BCS), requires criteria adjustments. The usefulness of computational simulation and modeling for extrapolation of adult data to paediatrics has been confirmed as a tool for predicting drug formulation performance. Despite the great number of successful physiologically based pharmacokinetic models to simulate drug disposition, the simulation of drug absorption from the GI tract is a complicating issue in paediatric populations.
The biopharmaceutics tools for investigation of oral drug absorption in paediatrics need further development, refinement and validation. A combination of in vitro and in silico methods could compensate for the uncertainties accompanying each method on its own.
本综述讨论了目前用于评估儿科口服制剂性能的生物制药方法。
儿科胃肠道（GI）在其发育和生长过程中经历了许多形态和生理变化。一些生理参数尚未得到研究，这限制了现有体外生物制药工具预测儿科制剂体内性能的应用。膳食及其给药频率在儿童期不断发展，影响口服药物吸收。此外，基于成人生物药剂学分类系统（BCS）建立儿科生物药剂学分类系统（pBCS）需要调整标准。计算模拟和建模对于将成人数据外推至儿科的用途已被确认为预测药物制剂性能的工具。尽管有许多成功的基于生理学的药代动力学模型可用于模拟药物处置，但从胃肠道吸收药物的模拟在儿科人群中是一个复杂的问题。
用于研究儿科口服药物吸收的生物制药工具需要进一步开发、改进和验证。体外和计算方法的结合可以弥补每种方法自身存在的不确定性。
