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

• Published in: Journal of clinical pharmacology Vol. 61; no. 7; p. 913
• 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: Journal Article
• Language: English
• Published: England 01.07.2021
• Subjects: Adult; Amoxicillin - administration & dosage; Amoxicillin - pharmacokinetics; Amoxicillin - pharmacology; Area Under Curve; Benzene Derivatives - administration & dosage; Benzene Derivatives - pharmacokinetics; Benzene Derivatives - pharmacology; Clarithromycin - administration & dosage; Clarithromycin - analogs & derivatives; Clarithromycin - metabolism; Clarithromycin - pharmacokinetics; Clarithromycin - pharmacology; Dose-Response Relationship, Drug; Drug Combinations; 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; pharmacokinetics; drug interaction; pharmacodynamics; tegoprazan
• ISSN: 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 C (2.2-fold) and AUC (2.7-fold) of tegoprazan and M1 (2.1- and 2.2-fold for C and AUC , respectively) compared with administration of tegoprazan alone. The C and AUC 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.