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.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Naproxen , Administration, Oral , Area Under Curve , Benzene Derivatives , Celecoxib/adverse effects , Cross-Over Studies , Diclofenac/analogs & derivatives , Humans , Imidazoles , Male , Naproxen/adverse effects , Naproxen/pharmacokinetics , Republic of Korea , TabletsABSTRACT
Dapagliflozin, a selective sodium-glucose co-transporter-2 inhibitor, and linagliptin, a competitive, reversible dipeptidyl peptidase-4 inhibitor, are commonly prescribed antidiabetic medications in general clinics. Since there are several merits to combining them in a fixed-dose combination product, this study investigated the pharmacokinetic equivalence between the individual component (IC) and fixed-combination drug product (FCDP) forms of dapagliflozin and linagliptin. A randomized, open-label, single-dose crossover study was conducted. All participants (n = 48) were randomly allocated to group A (period 1: ICs, period 2: FCDP) or group B (period 1: FCDP, period 2: ICs), and each group received either a single dose of IN-C009 (FCDP) or single doses of both dapagliflozin and linagliptin. There was no statistically significant difference found between the pharmacokinetic variables of FCDP and IC. The values of estimated geometric mean ratios and the 90% confidence interval for both maximum concentration and area under the plasma drug concentration-time curve were within the range of 0.8-1.25 for both dapagliflozin and linagliptin. The results of the clinical study demonstrated comparable pharmacokinetic characteristics between IC and FCDP forms of dapagliflozin and linagliptin. The combined use of dapagliflozin and linagliptin was safe and tolerable in both formulations.
