<P><B>Abstract</B></P> <P>A physiologically-based pharmacokinetic (PBPK) model was developed for YH4808, a novel potassium-competitive acid blocker, using the SimCYP® Simulator based on the physicochemical, in vitro ...
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https://www.riss.kr/link?id=A107448701
2019
-
SCI,SCIE,SCOPUS
학술저널
1-10(10쪽)
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
<P><B>Abstract</B></P> <P>A physiologically-based pharmacokinetic (PBPK) model was developed for YH4808, a novel potassium-competitive acid blocker, using the SimCYP® Simulator based on the physicochemical, in vitro ...
<P><B>Abstract</B></P> <P>A physiologically-based pharmacokinetic (PBPK) model was developed for YH4808, a novel potassium-competitive acid blocker, using the SimCYP® Simulator based on the physicochemical, in vitro preclinical and clinical data of YH4808. The PBPK model was optimized using YH4808 concentrations obtained from the single-dose phase I clinical trial. Overall, the PBPK model adequately predicted the observed pharmacokinetic profiles of YH4808 in humans. The pharmacokinetic profiles of YH4808 after multiple oral administrations were predicted using a refined PBPK model. The ratios of model-predicted to observed C<SUB>max</SUB>, AUC<SUB>inf</SUB> and AUC<SUB>τ</SUB> values on Day 1 and Day 7 at 100 mg were 0.7–1.0. However, the model failed to predict a decreased exposure after multiple oral administration particularly at higher doses of 200 and 400 mg. The reduced solubility of YH4808 at higher pH was hypothesized as the main cause of the reduction in exposure such that absorption was decreased as pH was increased. This hypothesis was confirmed by PBPK modeling and simulation, where intragastric pH was increased by YH4808.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>