Integration of In Silico Pharmacokinetic Modeling Approaches Into In Vitro Dissolution Profiles to Predict Bioavailability of a Poorly Soluble Compound
作者: Takafumi KatoTomoyuki WatanabeKoichi NakamuraShuichi Ando
作者单位: 1Formulation Technology Research Laboratories, Pharmaceutical Technology Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan
2CMC Regulatory Affairs Department, Pharmaceutical Technology Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan
3Drug Metabolism & Pharmacokinetics Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan
刊名: Journal of Pharmaceutical Sciences, 2019
来源数据库: Elsevier Journal
DOI: 10.1016/j.xphs.2019.06.026
关键词: Poorly soluble compoundPharmacokineticsIn silico PK simulationAdvance compartmental absorption and transit modelGastroPlus TMIn vitro dissolutionPrediction accuracy
英文摘要: Abstract(#br)The objective of present study is to develop pharmacokinetic (PK) prediction methods using in silico PK model for oral immediate release drug products (i.e. solution, suspension, and amorphous solid dispersion). A poorly water soluble compound with low bioavailability in rat was used (CS-758 as a model compound). A constructed in silico PK model contained an advance compartmental absorption and transit model. For solution, the in silico PK model reproduced an observed rat plasma concentration (Cp)-time profile. In addition, an in vitro dissolution method was developed to predict a rat Cp-time profile for suspension. As a result, the in silico PK model could predict the observed one by using dissolution profiles as the input. Furthermore, a dissolution profile of amorphous...
全文获取路径: Elsevier  (合作)
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影响因子:3.13 (2012)

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