title: Potent acid inhibition by vonoprazan in comparison with esomeprazole, with reference to CYP2C19 genotype.
abstract: BACKGROUND
  Acid inhibitory effects of proton pump inhibitors (PPIs) are influenced by CYP2C19 genotype. In contrast, the potent acid inhibition of vonoprazan is not influenced by CYP2C19 genotype.
  
  
  OBJECTIVE
  To compare the acid inhibitory effects of vonoprazan and esomeprazole in relation to CYP2C19 genotype.
  
  
  METHODS
  Twenty-eight healthy Japanese volunteers [7 CYP2C19 poor metabolisers (PMs), 11 intermediate metabolisers (IMs) and 10 rapid metabolisers (RMs)] received four different regimens in a randomised crossover manner: (i) vonoprazan 20 mg twice daily (b.d.), (ii) vonoprazan 20 mg daily, (iii) esomeprazole 20 mg b.d. and (iv) esomeprazole 20 mg daily. The timing of each dosing was 1 h before a meal. Twenty-four-hour intragastric pH monitoring was performed on day 7 on each regimen.
  
  
  RESULTS
  In the overall genotype group, pH ≥4 holding time ratios (pH 4 HTRs) with vonoprazan b.d., vonoprazan daily, esomeprazole b.d. and esomeprazole daily were 100%, 95%, 91%, and 68% respectively. pH 5 HTRs were 99%, 91%, 84% and 54% respectively. Vonoprazan b.d. potently suppressed acid for 24 h, and was significantly superior to other regimens irrespective of CYP2C19 genotype. Vonoprazan daily was equivalent to esomeprazole b.d. in IMs and PMs, but superior in RMs. CYP2C19 genotype-dependent differences were observed in esomeprazole daily but not in vonoprazan b.d. or daily.
  
  
  CONCLUSIONS
  Vonoprazan 20 mg b.d. inhibits acid irrespective of CYP2C19 genotype, more potently than esomeprazole 20 mg b.d., pH 4 and 5 holding time ratios reached 100% and 99%, respectively.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kagami
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sahara
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ichikawa
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Uotani
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamade
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Department of Clinical Oncology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hamaya
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Iwaizumi
authors.affiliation: Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Osawa
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Miyajima
authors.affiliation: Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Furuta
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064098:Esomeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007564:Japan; D008297:Male; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: C552956:1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; D054328:Proton Pump Inhibitors; D011758:Pyrroles; D013449:Sulfonamides; D065731:Cytochrome P-450 CYP2C19; D064098:Esomeprazole