Pharmacokinetics and Pharmacodynamics of Tegoprazan Coadministered With Amoxicillin and Clarithromycin in Healthy Subjects

• Published in: Journal of clinical pharmacology 2021-07, Vol.61 (7), p.913-922
• Main Authors: Ghim, Jong‐Lyul, Chin, May Chien, Jung, Jinah, Lee, Jiwon, Kim, Seokuee, Kim, Bongtae, Song, Geun Seog, Choi, Young‐Kyung, Shin, Jae‐Gook
• Format: Article
• Language: English
• Subjects: Adult; Amoxicillin; Amoxicillin - administration & dosage; Amoxicillin - pharmacokinetics; Amoxicillin - pharmacology; Antibiotics; Area Under Curve; Benzene Derivatives - administration & dosage; Benzene Derivatives - pharmacokinetics; Benzene Derivatives - pharmacology; Clarithromycin; Clarithromycin - administration & dosage; Clarithromycin - analogs & derivatives; Clarithromycin - metabolism; Clarithromycin - pharmacokinetics; Clarithromycin - pharmacology; Dose-Response Relationship, Drug; Drug Combinations; drug interaction; Gastroesophageal reflux; Gastrointestinal Agents - administration & dosage; Gastrointestinal Agents - pharmacokinetics; Gastrointestinal Agents - pharmacology; Healthy Volunteers; Humans; Hydrogen-Ion Concentration; Imidazoles - administration & dosage; Imidazoles - pharmacokinetics; Imidazoles - pharmacology; Male; Metabolic Clearance Rate; Middle Aged; Penicillin; pH effects; Pharmacodynamics; Pharmacokinetics; tegoprazan; Ulcers
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1002/jcph.1805

This clinical trial was conducted to evaluate the pharmacokinetics and pharmacodynamics of tegoprazan when coadministered with amoxicillin/clarithromycin in healthy subjects. Cohort 1 was an open‐label, randomized multiple‐dose study to evaluate the mutual interaction of tegoprazan and amoxicillin/clarithromycin on the disposition of 3 tested drugs including tegoprazan M1 metabolite and 14‐hydroxyclarithromycin (14‐OH‐clarithromycin). Cohort 2 was an open‐label, randomized, active‐controlled, parallel multiple‐dose study to compare the intragastric pH profile after multiple oral doses of 50 or 100 mg tegoprazan coadministered with amoxicillin/clarithromycin 1000/500 mg for 7 days and pantoprazole‐based triple therapy as the comparator arm. The coadministration of tegoprazan with amoxicillin/clarithromycin increased Css,max (2.2‐fold) and AUCτ (2.7‐fold) of tegoprazan and M1 (2.1‐ and 2.2‐fold for Css,max and AUCτ, respectively) compared with administration of tegoprazan alone. The Css,max and AUCτ of 14‐OH‐clarithromycin increased by 1.7‐ and 1.8‐fold, respectively; the disposition of amoxicillin and clarithromycin were not significantly changed. On days 1 and 7 of treatment, tegoprazan‐based therapies (both 50‐ and 100‐mg therapies) maintained pH above 6 for more than 88% of the 24‐hour period, which was significantly longer compared with pantoprazole‐based therapy. Tegoprazan either alone or in combination with amoxicillin/clarithromycin was well tolerated in healthy subjects. In conclusion, the exposure of tegoprazan was increased after coadministration of amoxicillin/clarithromycin, which led to increase pharmacodynamic response measured by intragastric pH compared with tegoprazan alone. Therefore, tegoprazan‐based triple therapy would be effective therapeutic regimen to manage intragastric pH in terms of gastric or duodenal ulcers healing, treatment of gastroesophageal reflux disease, and Helicobacter pylori eradication.