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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Article info
Publication history
Published online: July 01, 2022
Accepted:
June 7,
2022
Identification
Copyright
© 2022 Elsevier Inc.
