Dataset Information

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.

SUBMITTER: Oh M

PROVIDER: S-EPMC10333645 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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

Oh Minkyung M Lee Heechan H Kim Seokuee S Kim Bongtae B Song Geun Seog GS Shin Jae-Gook JG Ghim Jong-Lyul JL

Translational and clinical pharmacology 20230627 2

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 <i>Helicobacter pylori</i>. 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 t ...[more]

PMID: 37440779

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Project description:BackgroundTransient lower esophageal sphincter relaxations (TLESRs) have been identified as a primary cause of reflux events in patients with gastroesophageal reflux disease (GERD). GABA(B) receptor agonists such as lesogaberan (AZD3355) have been shown to inhibit TLESRs in healthy subjects and patients with GERD, and, therefore, offer a novel therapeutic add-on strategy to acid suppression for the management of GERD. As lesogaberan is being developed as an add-on treatment for the management of patients with GERD who have a partial response to proton pump inhibitor (PPI) therapy, it is important to rule out any clinically important pharmacokinetic drug-drug interaction between lesogaberan and PPIs.ObjectiveTo evaluate the effect of esomeprazole on the pharmacokinetics and safety of lesogaberan and vice versa.Study designThis was an open-label, randomized, three-way crossover study. The study was open to healthy adult male and female subjects. The study subjects received treatment with, in random order, lesogaberan (150 mg twice daily [dose interval 12 hours]), esomeprazole (40 mg once daily), and a combination of both, during 7-day treatment periods.Main outcomeThe presence or absence of pharmacokinetic interactions between lesogaberan and esomeprazole was assessed by measuring the steady-state area under the plasma concentration-time curves during the dosing interval (AUC(τ)) and the maximum observed plasma concentration (C(max)) for lesogaberan and esomeprazole.ResultsThirty male subjects (mean age 23.2 years, 97% Caucasian) were randomized to treatment and 28 subjects completed the study (one subject was lost to follow-up, and one subject discontinued due to an adverse event). The 95% confidence intervals of the geometric mean ratios for AUC(τ) and C(max) of lesogaberan and esomeprazole administered alone and concomitantly were within the recognized boundaries of bioequivalence (0.8-1.25). No new safety concerns were raised during this study. The number of patients with adverse events during treatment with lesogaberan alone (n = 17) and concomitantly with esomeprazole (n = 18) were comparable but higher than with esomeprazole alone (n = 10). Paresthesia (episodic, mild, and transient), pharyngitis, and flatulence were the most frequently reported adverse events.ConclusionsThere was no observed pharmacokinetic interaction between lesogaberan and esomeprazole when concomitantly administered to healthy subjects, and concomitant therapy was well tolerated. TRIAL REGISTRATION NUMBER (clinicaltrials.gov): NCT00684190.

Dataset Information

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

Trial registration

Publications

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

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