Tegoprazan for nocturnal acid breakthrough: A comparative study

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Created On: 26/06/2025

Nocturnal acid breakthrough has long challenged the efficacy of proton pump inhibitors (PPIs), leaving a therapeutic gap in acid-related disorder management.

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Key take away

Tegoprazan provides the fastest, most sustained night-time acid suppression (independent of CYP2C19 phenotype) when compared to vonoprazan and esomeprazole.

Background

Nocturnal acid breakthrough has long challenged the efficacy of proton pump inhibitors (PPIs), leaving a therapeutic gap in acid-related disorder management. Tegoprazan, a new potassium-competitive acid blocker (P-CAB), has emerged as a promising candidate to fill this gap. This study sought to directly compare the night-time acid-suppressive capacity of tegoprazan with vonoprazan and esomeprazole, and to assess whether CYP2C19 phenotypes modulate these effects.

Method

In this randomized, open-label, 3-period, 6-sequence crossover design, 16 healthy participants (6 CYP2C19 extensive metabolizers, 5 intermediate metabolizers, and 5 poor metabolizers) received a single nighttime dose of either tegoprazan 50 mg, vonoprazan 20 mg, or esomeprazole 40 mg across three study phases. Intragastric pH levels were continuously scrutinized throughout the night, and CYP2C19 metabolizer status was determined for all subjects.

Result

Tegoprazan achieved a faster and more stable rise in intragastric pH (≥4 within ~1 hour) compared to its counterparts. Night-time acid suppression was greatest with tegoprazan (66.0%), followed by vonoprazan (60.5%) and esomeprazole (36.1%). Notably, while esomeprazole’s efficacy fluctuated with CYP2C19 phenotype, both tegoprazan and vonoprazan maintained consistent effects across all metabolizer types.

Conclusion

When administered at bedtime, tegoprazan demonstrated faster onset, stronger, and more sustained night-time acid suppression compared to vonoprazan and esomeprazole, without influence from CYP2C19 phenotype. These findings support tegoprazan’s potential role in tackling nocturnal acid breakthrough.