Editorial: pharmacodynamics of potassium‐competitive acid blockers: comparing apples with apples – and with oranges. Authors’ reply

Abstract

We thank Dr Howden for his interest in our recent work.1,2 Our study showed a stronger effect of tegoprazan, a newly approved potassium-competitive acid blocker (P-CAB), on suppressing gastric acidity than revaprazan. Howden argued that the degree of suppression with tegoprazan was less than that for a proton pump inhibitor (PPI). However, we feel that the comparison with esomeprazole 20 mg twice daily was not appropriate since this is not an approved regimen for the treatment of gastro-oesophageal reflux disease. In the same study, intragastric pH above 4 (%Time pH ≥ 4) with esomeprazole 20 mg once-daily after multiple doses was 68%.3 Also, %Time pH ≥ 4 after multiple doses were 61.2% and 65.1% for esomeprazole 20 mg once-daily and rabeprazole 10 mg once-daily, respectively.4 Thus, the acid-suppressive effects of once-daily regimens of PPIs were similar to that of tegoprazan in our study (68.2%). As Howden mentioned, some P-CABs including AZD0865 failed to show superiority over PPIs for the treatment of acid-related disorders. However, both tegoprazan 50 mg and 100 mg once-daily showed non-inferiority to PPIs through phase III clinical trials in patients with erosive oesophagitis or gastric ulcer.5,6 In addition, vonoprazan, another P-CAB, has also shown effectiveness for the treatment of acid-related disorders.7,8 Although PPIs are good treatment options for acid-related disorders, there are several limitations including slow onset of action and poor compliance due to dosing time restrictions around meals and influence of CYP2C19 genotypes on efficacy.9 Tegoprazan shows sufficient intragastric acidity suppression within 1 hour from the first dose, no food effect on the efficacy, and is mainly metabolised by CYP3A, not CYP2C19.10 Therefore, tegoprazan is expected to meet the unmet need left by PPIs. Anyway, we need both apples and oranges.