Evaluation of pharmacokinetic drug-drug interaction between tegoprazan and clarithromycin in healthy subjects.

Abstract

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.