Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans
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 H<sub>2</sub> antagonists and proton pump inhibitors (PPIs), it would be i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/6/709 |
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| author | Min-Soo Kim Nora Lee Areum Lee Yoon-Jee Chae Suk-Jae Chung Kyeong-Ryoon Lee |
| author_facet | Min-Soo Kim Nora Lee Areum Lee Yoon-Jee Chae Suk-Jae Chung Kyeong-Ryoon Lee |
| author_sort | Min-Soo Kim |
| collection | DOAJ |
| description | 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 H<sub>2</sub> 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. |
| first_indexed | 2024-03-09T22:47:10Z |
| format | Article |
| id | doaj.art-239e5e671cc14f819957502655b87007 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:47:10Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-239e5e671cc14f819957502655b870072023-11-23T18:27:24ZengMDPI AGPharmaceuticals1424-82472022-06-0115670910.3390/ph15060709Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in HumansMin-Soo Kim0Nora Lee1Areum Lee2Yoon-Jee Chae3Suk-Jae Chung4Kyeong-Ryoon Lee5College of Pharmacy, Seoul National University, Seoul 08826, KoreaRIKEN Innovation Center, Research Cluster for Innovation, RIKEN, Yokohama 230-0045, Kanagawa, JapanDivision of Biopharmaceutics, College of Pharmacy, Kyung Hee University, Seoul 02447, KoreaCollege of Pharmacy, Woosuk University, Wanju-gun 55338, KoreaCollege of Pharmacy, Seoul National University, Seoul 08826, KoreaLaboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, KoreaFexuprazan 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 H<sub>2</sub> 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.https://www.mdpi.com/1424-8247/15/6/709DWP14012fexuprazanmodel-informed drug developmentpharmacodynamic modelingpharmacokinetic modelingpotassium-competitive acid blocker |
| spellingShingle | Min-Soo Kim Nora Lee Areum Lee Yoon-Jee Chae Suk-Jae Chung Kyeong-Ryoon Lee Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans Pharmaceuticals DWP14012 fexuprazan model-informed drug development pharmacodynamic modeling pharmacokinetic modeling potassium-competitive acid blocker |
| title | Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans |
| title_full | Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans |
| title_fullStr | Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans |
| title_full_unstemmed | Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans |
| title_short | Model-Based Prediction of Acid Suppression and Proposal of a New Dosing Regimen of Fexuprazan in Humans |
| title_sort | model based prediction of acid suppression and proposal of a new dosing regimen of fexuprazan in humans |
| topic | DWP14012 fexuprazan model-informed drug development pharmacodynamic modeling pharmacokinetic modeling potassium-competitive acid blocker |
| url | https://www.mdpi.com/1424-8247/15/6/709 |
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