Comparison of effect of an increased dosage of vonoprazan versus vonoprazan plus lafutidine on gastric acid inhibition and serum gastrin
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Vonoprazan, a novel potassium-competitive acid blocker, elicits potent acid inhibition and hypergastrinemia at a dose of 20 mg. Its recommended maintenance dose for gastro-esophageal reflux disease is 10 mg, which is sometimes insufficient for preventing nocturnal acid breakthrough (NAB). Concomitant use of a histamine 2 receptor antagonist (H2RA) is effective for NAB. However, further acid inhibition by addition of H2RA has concern of hypergastrinemia again. Lafutidine (H2RA) is known to stimulate somatostatin release.
The aim of this study is to compare the levels of acid inhibition and serum gastrin attained by addition of lafutidine to vonoprazan 10 mg with levels after a dose increase of vonoprazan from 10 to 20 mg.
Thirteen healthy volunteers underwent 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg.
Median pH 4 holding time ratios (range) by vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg were 82% (47–88%), 88% (76–93%), and 99% (95–100%) while those at nighttime from 10 p.m. to 8 a.m. were 94% (29–100%), 100% (95–100%), and 100%, respectively. The incidences of NAB with vonoprazan 10 mg, vonoprazan plus lafutidine, and vonoprazan 20 mg were 38, 8, and 0%, respectively. Respective serum gastrin levels were 420 (173–508), 323 (196–521), and 504 (400–812) pg/ml.
Addition of lafutidine 10 mg to vonoprazan 10 mg achieved sufficient acid inhibition, especially at nighttime, without further increase of serum gastrin levels.
KeywordsPotassium-competitive acid blocker Vonoprazan Lafutidine Histamine 2 receptor antagonist Intragastric pH
- pH 4 HRT
pH > 4 holding time ratio
Proton pump inhibitor
- 1.Sontag SJ (1990) The medical management of reflux esophagitis. Role of antacids and acid inhibition. Gastroenterol Clin N Am 19:683–712Google Scholar
- 16.Sugimoto M, Furuta T, Shirai N et al (2005) Comparison of an increased dosage regimen of rabeprazole versus a concomitant dosage regimen of famotidine with rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome P450 2C19 genotypes. Clin Pharmacol Ther 77:302–311CrossRefPubMedGoogle Scholar
- 19.Tari A, Yamamoto G, Sumii K et al (1993) Role of histamine 2 receptor in increased expression of rat gastric H(+)-K(+)-ATPase alpha-subunit induced by omeprazole. Am J Phys 265:G752–G758Google Scholar
- 23.Sano T, Utsumi D, Amagase K et al (2017) Lafutidine, a histamine H2 receptor antagonist with mucosal protective properties, attenuates 5-fluorouracil-induced intestinal mucositis in mice through activation of extrinsic primary afferent neurons. J Physiol Pharmacol: Off J Polish Physiol Soc 68:79–90Google Scholar
- 27.Sugano K (2015) Vonoprazan: a novel potassium-competitive acid blocker. Nihon rinsho Jpn J Clin Med 73:1163–1168Google Scholar
- 28.Lanzon-Miller S, Pounder RE, Chronos NA, Raymond F, Hamilton MR, Dalgleish D (1988) Twenty four hour intragastric acidity and plasma gastrin concentration in healthy volunteers taking nizatidine 150 mg, nizatidine 300 mg, ranitidine 300 mg, or placebo at 21:00 h. Gut 29:1364–1369CrossRefPubMedPubMedCentralGoogle Scholar