生物制药分类系统
溶解度
生物制药
化学
药品
胶束
体外
磁导率
药理学
色谱法
食品科学
生物化学
医学
生物活性
有机化学
水溶液
膜
生药学
作者
Konstantinos Stamatopoulos,Paola Ferrini,Dung N. Nguyen,Ying Zhang,James Butler,Jon G. Hall,Nena Mistry
出处
期刊:Pharmaceutics
[MDPI AG]
日期:2023-02-03
卷期号:15 (2): 521-521
被引量:3
标识
DOI:10.3390/pharmaceutics15020521
摘要
A strategy followed to integrate in vitro solubility and permeability data into a PBBM model to predict the food effect of a BCS IV zwitterionic drug (GSK3640254) observed in clinical studies is described. The PBBM model was developed, qualified and verified using clinical data of an immediate release (IR)-tablet (10-320 mg) obtained in healthy volunteers under fasted and fed conditions. The solubility of GSK3640254 was a function of its ionization state, the media composition and pH, whereas its permeability determined using MDCK cell lines was enhanced by the presence of mixed micelles. In vitro data alongside PBBM modelling suggested that the positive food effect observed in the clinical studies was attributed to micelle-mediated enhanced solubility and permeability. The biorelevant media containing oleic acid and cholesterol in fasted and fed levels enabled the model to appropriately capture the magnitude of the food effect. Thus, by using Simcyp® v20 software, the PBBM model accurately predicted the results of the food effect and predicted data were within a two-fold error with 70% being within 1.25-fold. The developed model strategy can be effectively adopted to increase the confidence of using PBBM models to predict the food effect of BCS class IV drugs.
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