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Evaluation of pharmacokinetic drug-drug interaction between tegoprazan and clarithromycin in healthy subjects
Tegoprazan is a novel potassium-competitive acid blocker that treats gastric acid-related diseases. Clarithromycin was widely used as one of various regimens for eradicating Helicobacter pylori. This study compared the pharmacokinetic and safety profile of tegoprazan and clarithromycin between combi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Clinical Pharmacology and Therapeutics
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333645/ https://www.ncbi.nlm.nih.gov/pubmed/37440779 http://dx.doi.org/10.12793/tcp.2023.31.e11 |
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author | Oh, Minkyung Lee, Heechan Kim, Seokuee Kim, Bongtae Song, Geun Seog Shin, Jae-Gook Ghim, Jong-Lyul |
author_facet | Oh, Minkyung Lee, Heechan Kim, Seokuee Kim, Bongtae Song, Geun Seog Shin, Jae-Gook Ghim, Jong-Lyul |
author_sort | Oh, Minkyung |
collection | PubMed |
description | Tegoprazan is a novel potassium-competitive acid blocker that treats gastric acid-related diseases. Clarithromycin was widely used as one of various regimens for eradicating Helicobacter pylori. This study compared the pharmacokinetic and safety profile of tegoprazan and clarithromycin between combination therapy and monotherapy to evaluate the potential drug-drug interaction. An open-label, randomized, 6-sequence, 3-period crossover study was conducted in 24 healthy subjects. According to the assigned sequence, the subject was administered the assigned treatment during 5 days in each period. PK parameters of tegoprazan and clarithromycin administered in combination were compared with those of the respective monotherapies. The co-administration of tegoprazan with clarithromycin increased maximum steady-state plasma concentration (C(ss,max)) and area under the plasma concentration-time curve in dosing interval at steady-state (AUC(ss,tau)) of tegoprazan (1.6-fold in C(ss,max) and 2.5-fold in AUC(ss,tau)) and M1 (2.0-fold in C(ss,max), 2.5-fold in AUC(ss,tau)) than tegoprazan alone. The C(ss,max) and AUC(ss,tau) of 14-hydroxyclarithromycin increased 1.8- and 2.0-fold in co-administration, respectively. The AUC(ss.tau) of clarithromycin was slightly increased in co-administration, but C(ss,max) was not changed. Combination of tegoprazan and clarithromycin and those of the respective monotherapies were tolerated in 24 healthy subjects. There may exist drug interaction that lead to reciprocal increase in plasma drug concentrations when tegoprazan and clarithromycin were administrated in combination and no safety concerns were raised. It is suggested that an in-depth analysis of the concentration-response relationship is necessary to determine whether these concentration changes warrant clinical action. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02052336 |
format | Online Article Text |
id | pubmed-10333645 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Korean Society for Clinical Pharmacology and Therapeutics |
record_format | MEDLINE/PubMed |
spelling | pubmed-103336452023-07-12 Evaluation of pharmacokinetic drug-drug interaction between tegoprazan and clarithromycin in healthy subjects Oh, Minkyung Lee, Heechan Kim, Seokuee Kim, Bongtae Song, Geun Seog Shin, Jae-Gook Ghim, Jong-Lyul Transl Clin Pharmacol Original Article Tegoprazan is a novel potassium-competitive acid blocker that treats gastric acid-related diseases. Clarithromycin was widely used as one of various regimens for eradicating Helicobacter pylori. This study compared the pharmacokinetic and safety profile of tegoprazan and clarithromycin between combination therapy and monotherapy to evaluate the potential drug-drug interaction. An open-label, randomized, 6-sequence, 3-period crossover study was conducted in 24 healthy subjects. According to the assigned sequence, the subject was administered the assigned treatment during 5 days in each period. PK parameters of tegoprazan and clarithromycin administered in combination were compared with those of the respective monotherapies. The co-administration of tegoprazan with clarithromycin increased maximum steady-state plasma concentration (C(ss,max)) and area under the plasma concentration-time curve in dosing interval at steady-state (AUC(ss,tau)) of tegoprazan (1.6-fold in C(ss,max) and 2.5-fold in AUC(ss,tau)) and M1 (2.0-fold in C(ss,max), 2.5-fold in AUC(ss,tau)) than tegoprazan alone. The C(ss,max) and AUC(ss,tau) of 14-hydroxyclarithromycin increased 1.8- and 2.0-fold in co-administration, respectively. The AUC(ss.tau) of clarithromycin was slightly increased in co-administration, but C(ss,max) was not changed. Combination of tegoprazan and clarithromycin and those of the respective monotherapies were tolerated in 24 healthy subjects. There may exist drug interaction that lead to reciprocal increase in plasma drug concentrations when tegoprazan and clarithromycin were administrated in combination and no safety concerns were raised. It is suggested that an in-depth analysis of the concentration-response relationship is necessary to determine whether these concentration changes warrant clinical action. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02052336 Korean Society for Clinical Pharmacology and Therapeutics 2023-06 2023-06-27 /pmc/articles/PMC10333645/ /pubmed/37440779 http://dx.doi.org/10.12793/tcp.2023.31.e11 Text en Copyright © 2023 Translational and Clinical Pharmacology https://creativecommons.org/licenses/by-nc/4.0/It is identical to the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/). |
spellingShingle | Original Article Oh, Minkyung Lee, Heechan Kim, Seokuee Kim, Bongtae Song, Geun Seog Shin, Jae-Gook Ghim, Jong-Lyul Evaluation of pharmacokinetic drug-drug interaction between tegoprazan and clarithromycin in healthy subjects |
title | Evaluation of pharmacokinetic drug-drug interaction between tegoprazan and clarithromycin in healthy subjects |
title_full | Evaluation of pharmacokinetic drug-drug interaction between tegoprazan and clarithromycin in healthy subjects |
title_fullStr | Evaluation of pharmacokinetic drug-drug interaction between tegoprazan and clarithromycin in healthy subjects |
title_full_unstemmed | Evaluation of pharmacokinetic drug-drug interaction between tegoprazan and clarithromycin in healthy subjects |
title_short | Evaluation of pharmacokinetic drug-drug interaction between tegoprazan and clarithromycin in healthy subjects |
title_sort | evaluation of pharmacokinetic drug-drug interaction between tegoprazan and clarithromycin in healthy subjects |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333645/ https://www.ncbi.nlm.nih.gov/pubmed/37440779 http://dx.doi.org/10.12793/tcp.2023.31.e11 |
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