Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy Subjects

Abstract

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.

Keywords: aspirin; drug interactions; fexuprazan; gastrointestinal complications; potassium-competitive acid blocker.

Figure 1

Platelet aggregation-time profiles obtained after a single oral administration of aspirin 500 mg with and without the coadministration of fexuprazan 80 mg in (A) arachidonic acid-induced assay and in (B) collagen-induced assay. The error bars represent the standard deviations.

Figure 2

Maximum arachidonic acid-induced and collagen-induced platelet aggregation (%) measured after a single oral administration of aspirin 500 mg alone and coadministered with fexuprazan 80 mg. The horizontal lines, vertical lines, and symbols represent the median, minimum-to-maximum, and individual data, respectively.

Figure 3

Mean plasma concentration-time profiles of (A) aspirin and (B) salicylic acid measured after a single oral administration of aspirin 500 mg alone and coadministered with fexuprazan 80 mg. The error bars represent the standard deviations.

Figure 4

Mean plasma concentration-time profiles of (A) fexuprazan and (B) M14 measured after multiple oral administrations of fexuprazan 80 mg alone and coadministered with aspirin 500 mg. The error bars represent the standard deviations.