Model-based prediction of acid suppression and proposal of a new dosing regimen of fexuprazan in humans

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Title
Model-based prediction of acid suppression and proposal of a new dosing regimen of fexuprazan in humans
Author(s)
M S Kim; N Lee; A Lee; Y J Chae; S J Chung; Kyeong-Ryoon Lee
Bibliographic Citation
Pharmaceuticals, vol. 15, no. 6, pp. 709-709
Publication Year
2022
Abstract
Fexuprazan is a potassium-competitive acid blocker (P-CAB). The compounds in this newly developed drug family suppress intragastric acidity. As there are already other acid-suppressing drugs on the market, such as H2 antagonists and proton pump inhibitors (PPIs), it would be informative to compare the biological effects of fexuprazan against another approved drug with the same indication. The drug concentration predicted by the pharmacokinetic (PK) model could serve as an input function for a pharmacodynamic (PD) model. The apparent pharmacokinetics of fexuprazan could be described by a simpler model. However, a physiologically based pharmacokinetic (PBPK) model was developed in a previous study. A one-compartment model was also proposed in the present study. Both the newly suggested model and the previously validated PBPK model were used as input functions of the PD models. Our simulation revealed that the effects of fexuprazan could be effectively simulated by the proposed PK-PD models. A PK-PD model was also proposed for the oral administration of the PPI reference drug esomeprazole. A model-based analysis was then performed for intragastric pH using several dosing methods. The expected pH could be predicted for both drugs under several dosing regimens using the proposed PK-PD models.
Keyword
DWP14012FexuprazanModel-informed drug developmentPharmacodynamic modelingPharmacokinetic modelingPotassium-competitive acid blocker
ISSN
1424-8247
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/ph15060709
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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