Pharmacokinetic Interactions between Tegoprazan and Metronidazole/Tetracycline/Bismuth and Safety Assessment in Healthy Korean Male Subjects.

Abstract

PURPOSE\nTegoprazan is a potassium-competitive acid blocker used for gastric acid suppression, which may be used with Helicobacter pylori eradication therapies. The goal of this study was to evaluate the pharmacokinetic interaction between tegoprazan and triple-antibiotic therapy containing metronidazole, tetracycline, and bismuth.\n\n\nMETHODS\nAn open-label, 2-cohort, randomized, multiple-dose, crossover study was conducted in healthy subjects. In cohort 1, tegoprazan (100\xa0mg/d) was administered orally with or without triple-antibiotic therapy (1500\xa0mg/d metronidazole, 2000\xa0mg/d tetracycline, and 1200\xa0mg/d bismuth) for 7 days in each period. In cohort 2, triple-antibiotic therapy was administered orally with or without tegoprazan for 7 days in each period. Pharmacokinetic blood samples were collected within 24\xa0h after the last dose. Safety assessments were performed.\n\n\nFINDINGS\nEleven cohort 1 subjects and ten cohort 2 subjects were included in the pharmacokinetic analysis. The AUCτ and Cmax at steady state geometric mean ratios (90% CIs) were 0.78 (0.73-0.83) and 0.75 (0.68-0.82) for tegoprazan; 0.77 (0.68-0.88) and 0.84 (0.72-0.98) for tegoprazan metabolite M1; 1.03 (0.98-1.08) and 1.08 (0.99-1.18) for metronidazole; 0.63 (0.56-0.70) and 0.64 (0.56-0.74) for tetracycline; and 1.55 (0.99-2.44) and 1.38 (0.72-2.66) for bismuth, respectively. All reported adverse events were mild.\n\n\nIMPLICATIONS\nChanges in the tegoprazan, tetracycline, and bismuth pharmacokinetic parameters were detected after concurrent administration. These changes were considered mainly due to the pharmacodynamic effect of tegoprazan. The adverse events were predictable and reported as frequent adverse events during triple-antibiotic therapy. There were no significant differences in safety or tolerability between quadruple therapy, including tegoprazan and triple-antibiotic therapy. ClinicalTrials.gov identifier: NCT04066257.