생리학 기반 약물동태(PBPK, Physiologically Based Pharmacokinetic) 모델링을 이용한 소아 약물 동태 예측 연구

Application of Physiologically Based Pharmacokinetic (PBPK) Modeling in Prediction of Pediatric Pharmacokinetics

In recent years, physiologically based pharmacokinetic (PBPK) modeling has been widely used in pharmaceutical industries as well as regulatory health authorities for drug discovery and development. Several application areas of PBPK have been introduced so far including drug-drug interaction prediction, transporter-mediated interaction prediction, and pediatric PK prediction. The purpose of this review is to introduce PBPK and illustrates one of its application areas, particularly pediatric PK prediction by utilizing existing adult PK data and in vitro data. The evaluation of the initial PBPK for adult was done by comparing with experimental PK profiles and the scaling from adult to pediatric was conducted using age-related changes in size such as tissue compartments, and protein binding etc. Sotalol and lorazepam were selected in this review as model drugs for this purpose and were re-evaluated using the PBPK models by GastroPlus？？. The challenges and strategies of PBPK models using adult PK data as well as appropriate in vitro assay data for extrapolating pediatric PK at various ages were also discussed in this paper.