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Pharmacokinetics and Pharmacodynamics of Tegoprazan Coadministered With Amoxicillin and Clarithromycin in Healthy Subjects
Author(s) -
Ghim JongLyul,
Chin May Chien,
Jung Jinah,
Lee Jiwon,
Kim Seokuee,
Kim Bongtae,
Song Geun Seog,
Choi YoungKyung,
Shin JaeGook
Publication year - 2021
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1805
Subject(s) - clarithromycin , amoxicillin , pharmacokinetics , pharmacology , medicine , pharmacodynamics , antibacterial agent , drug interaction , antibiotics , chemistry , helicobacter pylori , biochemistry
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 ss,max (2.2‐fold) and AUC τ (2.7‐fold) of tegoprazan and M1 (2.1‐ and 2.2‐fold for C ss,max and AUC τ , respectively) compared with administration of tegoprazan alone. The C ss,max and AUC τ 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.