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Pharmacokinetic Interactions Between Tegoprazan and Naproxen, Aceclofenac, and Celecoxib in Healthy Korean Male Subjects

  • Seol Ju Moon
    Affiliations
    Center for Clinical Pharmacology and Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju, Republic of Korea

    Research Institute of Clinical Medicine of Jeonbuk National University, Jeonju, Republic of Korea

    Department of Pharmacology, School of Medicine, Jeonbuk National University, Jeonju, Republic of Korea
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  • Naree Shin
    Affiliations
    Division of Clinical Development, HK inno.N Corp, Seoul, Republic of Korea
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  • MinJa Kang
    Affiliations
    Division of Clinical Development, HK inno.N Corp, Seoul, Republic of Korea
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  • Bongtae Kim
    Affiliations
    Division of Clinical Development, HK inno.N Corp, Seoul, Republic of Korea
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  • Min-Gul Kim
    Correspondence
    Address correspondence to: Min-Gul Kim, MD, PhD, Department of Pharmacology, School of Medicine, Jeonbuk National University, 20 Geonji-ro, Deokjin-gu, Jeonju, Republic of Korea
    Affiliations
    Center for Clinical Pharmacology and Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju, Republic of Korea

    Research Institute of Clinical Medicine of Jeonbuk National University, Jeonju, Republic of Korea

    Department of Pharmacology, School of Medicine, Jeonbuk National University, Jeonju, Republic of Korea
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      Abstract

      Purpose

      Tegoprazan is a potassium-competitive acid blocker used for gastric acid suppression and may be used with NSAIDs to reduce gastrointestinal adverse effects. The aim of this study was to evaluate the pharmacokinetic interaction between tegoprazan and commonly used NSAIDS, namely, naproxen, aceclofenac, and celecoxib.

      Methods

      An open-label, 3-cohort, randomized, multiple-dose, 3-way crossover study was conducted in healthy male subjects. In cohort 1, tegoprazan (50-mg tablet, once daily) and naproxen (500-mg tablet, twice daily) were administered separately or concurrently for 7 days in each period. In cohort 2, tegoprazan and aceclofenac (100-mg tablet, twice daily) were administered separately or concurrently for 7 days in each period. In cohort 3, tegoprazan and celecoxib (200-mg capsule, twice daily) were administered separately or concurrently for 7 days in each period. Pharmacokinetic blood samples were collected up to 24 hours after the last dose.

      Findings

      Seventeen subjects from cohort 1, sixteen subjects from cohort 2, and thirteen subjects from cohort 3 were included in the pharmacokinetic analysis. In cohort 1, the geometric least squares mean ratios (90% CIs) for AUCτ (AUC profiles over the dosing interval) and Css,max (Cmax at steady state) were 1.01 (0.91–1.12) and 0.99 (0.83–1.17) for tegoprazan, and 1.00 (0.97–1.03) and 1.04 (0.99–1.09) for naproxen, respectively. The values in cohort 2 were 1.03 (0.93–1.13) and 0.94 (0.86–1.04) for tegoprazan, and 1.06 (1.00–1.12) and 1.31 (1.08–1.60) for aceclofenac. The values in cohort 3 were 1.01 (0.86–1.18) and 1.02 (0.87–1.19) for tegoprazan, and 1.08 (0.96–1.22) and 1.18 (0.97–1.43) for celecoxib.

      Implications

      Changes in the maximum aceclofenac or celecoxib concentrations were detected after concurrent administration with tegoprazan, which were considered mainly due to the pharmacodynamic effect of tegoprazan. Because systemic drug exposure (shown as AUCτ) was unchanged after concurrent administration of any 3 NSAIDs with tegoprazan, the increase in aceclofenac or celecoxib Css,max when administered with tegoprazan would not be clinically significant in practice. ClinicalTrials.gov Identifier: NCT04639804.

      Key words

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