Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy Subjects
Acid-reducing agents are commonly used for the prevention of aspirin-induced gastrointestinal complications such as peptic ulcers. As a novel potassium-competitive acid blocker, fexuprazan is expected to prevent aspirin-induced gastrointestinal complications. This randomized, open-label study aimed...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Online Access: | https://www.mdpi.com/1999-4923/15/2/549 |
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| author | JungJin Oh Eunsol Yang In-Jin Jang Hyejung Lee Hokyun Yoo Jae-Yong Chung SeungHwan Lee Jaeseong Oh |
| author_facet | JungJin Oh Eunsol Yang In-Jin Jang Hyejung Lee Hokyun Yoo Jae-Yong Chung SeungHwan Lee Jaeseong Oh |
| author_sort | JungJin Oh |
| collection | DOAJ |
| description | Acid-reducing agents are commonly used for the prevention of aspirin-induced gastrointestinal complications such as peptic ulcers. As a novel potassium-competitive acid blocker, fexuprazan is expected to prevent aspirin-induced gastrointestinal complications. This randomized, open-label study aimed to evaluate the pharmacodynamic and pharmacokinetic interactions between aspirin and fexuprazan in healthy Koreans. Subjects randomized to the aspirin group received 500 mg aspirin in combination with 80 mg fexuprazan. For the fexuprazan group, fexuprazan 80 mg was administered alone and then in combination with aspirin 500 mg. Platelet aggregation inhibited by aspirin and the pharmacokinetic parameters of aspirin and fexuprazan were compared between monotherapy and combination therapy. A total of 22 subjects completed the study. The platelet aggregation-inhibitory activity and systemic exposure to aspirin were not significantly affected by fexuprazan coadministration. The systemic exposure of fexuprazan was decreased up to 20% by aspirin coadministration, which was not regarded as clinically meaningful considering the previously reported exposure–response relationship. In conclusion, there were no clinically relevant pharmacodynamic or pharmacokinetic interactions between aspirin and fexuprazan. This finding suggests the potential of fexuprazan for the prevention of aspirin-induced gastrointestinal complications, serving as a baseline for optimizing its therapeutic application with aspirin. |
| first_indexed | 2024-03-11T08:17:12Z |
| format | Article |
| id | doaj.art-b0876cdc2d6f4a53b47df5aecce0a5fe |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T08:17:12Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b0876cdc2d6f4a53b47df5aecce0a5fe2023-11-16T22:41:25ZengMDPI AGPharmaceutics1999-49232023-02-0115254910.3390/pharmaceutics15020549Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy SubjectsJungJin Oh0Eunsol Yang1In-Jin Jang2Hyejung Lee3Hokyun Yoo4Jae-Yong Chung5SeungHwan Lee6Jaeseong Oh7Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of KoreaDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of KoreaDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of KoreaDaewoong Pharmaceutical Co., Ltd., Seoul 06170, Republic of KoreaDaewoong Pharmaceutical Co., Ltd., Seoul 06170, Republic of KoreaDepartment of Clinical Pharmacology and Therapeutics, Seoul National University Bundang Hospital, Seongnam 13620, Republic of KoreaDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of KoreaDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of KoreaAcid-reducing agents are commonly used for the prevention of aspirin-induced gastrointestinal complications such as peptic ulcers. As a novel potassium-competitive acid blocker, fexuprazan is expected to prevent aspirin-induced gastrointestinal complications. This randomized, open-label study aimed to evaluate the pharmacodynamic and pharmacokinetic interactions between aspirin and fexuprazan in healthy Koreans. Subjects randomized to the aspirin group received 500 mg aspirin in combination with 80 mg fexuprazan. For the fexuprazan group, fexuprazan 80 mg was administered alone and then in combination with aspirin 500 mg. Platelet aggregation inhibited by aspirin and the pharmacokinetic parameters of aspirin and fexuprazan were compared between monotherapy and combination therapy. A total of 22 subjects completed the study. The platelet aggregation-inhibitory activity and systemic exposure to aspirin were not significantly affected by fexuprazan coadministration. The systemic exposure of fexuprazan was decreased up to 20% by aspirin coadministration, which was not regarded as clinically meaningful considering the previously reported exposure–response relationship. In conclusion, there were no clinically relevant pharmacodynamic or pharmacokinetic interactions between aspirin and fexuprazan. This finding suggests the potential of fexuprazan for the prevention of aspirin-induced gastrointestinal complications, serving as a baseline for optimizing its therapeutic application with aspirin.https://www.mdpi.com/1999-4923/15/2/549drug interactionsaspirinfexuprazanpotassium-competitive acid blockergastrointestinal complications |
| spellingShingle | JungJin Oh Eunsol Yang In-Jin Jang Hyejung Lee Hokyun Yoo Jae-Yong Chung SeungHwan Lee Jaeseong Oh Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy Subjects Pharmaceutics drug interactions aspirin fexuprazan potassium-competitive acid blocker gastrointestinal complications |
| title | Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy Subjects |
| title_full | Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy Subjects |
| title_fullStr | Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy Subjects |
| title_full_unstemmed | Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy Subjects |
| title_short | Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy Subjects |
| title_sort | pharmacodynamic and pharmacokinetic drug interactions between fexuprazan a novel potassium competitive inhibitor and aspirin in healthy subjects |
| topic | drug interactions aspirin fexuprazan potassium-competitive acid blocker gastrointestinal complications |
| url | https://www.mdpi.com/1999-4923/15/2/549 |
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