Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial

An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14–20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21–27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period.

The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (C_max,ss) and area under the plasma concentration–time curve over the dosing interval (AUC_τ) at steady state were 195.93% (175.52–218.71%) and 287.54% (263.28–314.04%) for tegoprazan and 423.23% (382.57–468.22%) and 385.61% (354.62–419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of C_max,ss and AUC_τ were 83.69% (77.44–90.45%) and 110.30% (102.74–118.41%) for clarithromycin, 126.25% (114.73–138.93%) and 146.94% (135.33–159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73–82.60%) and 94.34% (87.94–101.20%) for amoxicillin, and 158.43% (125.43–200.11%) and 183.63% (156.42–215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages.

The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability.

CTR20230643.