Evaluation of CYP2C19-Mediated Pharmacokinetic Drug Interaction of Tegoprazan, Compared with Vonoprazan or Esomeprazole

Abstract

Background and Objective CYP2C19-mediated drug interactions of acid-reducing agents are clinically important given the high possibility of concomitant administration with CYP2C19 substrates. This study aimed to evaluate the effect of tegoprazan on the pharmacokinetics (PK) of a CYP2C19 substrate, proguanil, compared with vonoprazan or esomeprazole. Methods A two-part, randomized, open-label, two-sequence, three-period crossover study was conducted in 16 healthy CYP2C19 extensive metabolizers (eight subjects per part). In each period, a single oral dose of atovaquone/proguanil 250/100 mg was administered alone or co-administered with tegoprazan 50 mg, esomeprazole 40 mg (Part 1 only) or vonoprazan 20 mg (Part 2 only). The plasma and urine concentrations of proguanil and its metabolite, cycloguanil, were measured up to 48 h post-dose. PK parameters were calculated using a non-compartmental method and compared between administered alone and co-administered with tegoprazan, vonoprazan or esomeprazole. Results Co-administration of tegoprazan did not significantly affect the systemic exposure of proguanil and cycloguanil. In contrast, co-administration of vonoprazan or esomeprazole increased proguanil systemic exposure and decreased cycloguanil systemic exposure, and the magnitude of the corresponding change was greater with esomeprazole co-administration than vonoprazan co-administration. Conclusion Tegoprazan, unlike vonoprazan and esomeprazole, exhibited negligible CYP2C19-mediated PK interaction. It suggests that as an alternative to other acid-reducing agents, tegoprazan can be used concomitantly with CYP2C19 substrates in clinical settings. Trial Registration Clinicaltrials.gov identifier: NCT04568772 (Registered on September 29, 2020).

Fourteen‐Day Tegoprazan–Amoxicillin Dual Therapy as the First‐Line Treatment of Helicobacter pylori Infection (SHARE2301): A Multicenter, Noninferiority, Randomized Clinical Trial

“…Different from PPIs, P‐CABs were characterized by a rapid onset of action, a predictable antisecretory profile, and are not dependent on CYP2C19 genotype. Unlike esomeprazole and vonoprazan, pharmacokinetic studies have demonstrated that tegoprazan exhibits negligible CYP2C19 ‐mediated PK interactions, which may allow tegoprazan to be used concomitantly with CYP2C19 substrates [8]. In triple and bismuth‐containing quadruple therapies, PPI‐based regimens demonstrated similar efficacy to regimens on the basis of tegoprazan [9, 10].…”

“…Potassium‐competitive acid blockers (P‐CABs), represented by vonoprazan, have shown satisfactory efficacy in the eradication of H. pylori in dual therapy [7]. Tegoprazan, a novel type of P‐CABs, was shown to have comparable acid inhibitory capacity to vonoprazan by pharmacokinetics [8]. Its efficacy in eradicating H. pylori in bismuth‐containing quadruple therapy has been preliminarily demonstrated, but remains unelaborated in dual therapy [9].…”

Vonoprazan: a promising advancement in proton pump inhibitor therapy

“…In contrast to conventional inhibitors of the proton pump (PPIs), which need an acidic environment to be active, vonoprazan can inhibit acid secretion in both acidic and non-acidic conditions. 5 Vonoprazan has been demonstrated to raise gastric pH levels more effectively and for a longer duration than some conventional PPIs. It has also demonstrated efficacy in promoting the healing of gastric and duodenal ulcers, as well as in preventing nonsteroidal anti-inflammatory drug (NSAID)-induced gastroduodenal injury.…”