Key result
Co-administration of tegoprazan and clarithromycin increased the steady-state area under the curve of tegoprazan by 2.5-fold compared to tegoprazan alone.
Why the study?
This study compared the pharmacokinetic and safety profile of tegoprazan and clarithromycin between combination therapy and monotherapy to evaluate their potential drug-drug interaction.
Does co-administration of tegoprazan and clarithromycin alter their pharmacokinetic profiles compared to monotherapy in healthy subjects?
RCT (n=24)
Open-label
6-sequence, 3-period crossover
No
Does co-administration of tegoprazan and clarithromycin alter their pharmacokinetic profiles compared to monotherapy in healthy subjects?
Co-administration of tegoprazan and clarithromycin reciprocally increases plasma drug concentrations, suggesting a need for concentration-response analysis to determine clinical relevance.
Answers are grounded in this paper and cite their sources.
May warrant tegoprazan dose adjustment with clarithromycin; extends DDI data but leaves clinical relevance open.
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 (1.6fold 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 concentrationresponse relationship is necessary to determine whether these concentration changes warrant clinical action.
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Oh et al. (2023) conducted an RCT in Healthy subjects (n=24). Tegoprazan and clarithromycin co-administration vs. Tegoprazan 200 mg once daily alone was evaluated on Area under the plasma concentration-time curve in dosing interval at steady-state (AUCss,tau) of tegoprazan (GMR 2.50, 95% CI 2.3525-2.6538). Co-administration of tegoprazan and clarithromycin increased the steady-state area under the curve of tegoprazan by 2.5-fold compared to tegoprazan alone.
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