Vonoprazan pharmacokinetics and effects on gastric pH in horses

Vonoprazan pharmacokinetics and effects on gastric pH following administration to fed and fasted horses
Equine Vet J. 2026 Jan 14. doi: 10.1111/evj.70128. Online ahead of print.
Authors
Camilo J Morales 1 , Benjamin W Sykes 2 , Daniel S McKemie 1 , Philip H Kass 3 , Heather K Knych 1 4
Affiliations

1 K. L. Maddy Equine Analytical Chemistry Laboratory (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
2 BW Sykes Consultancy, Coffs Harbour, New South Wales, Australia.
3 Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
4 Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.

PMID: 41532453
DOI: 10.1111/evj.70128

Abstract

Background: Current treatment options for equine gastric ulcer syndrome (EGUS), such as omeprazole-a proton pump inhibitor (PPI)-have notable limitations, including the need for administration on an empty stomach. Potassium-competitive acid blockers (P-CABs), such as vonoprazan, are a newer class of acid suppressants that offer several advantages over PPIs in humans and may provide similar benefits in horses.

Objectives: To describe the pharmacokinetics and effect of a single oral dose of vonoprazan on intragastric pH in horses. We hypothesised that vonoprazan would follow linear kinetics across the doses studied and effectively increase intragastric pH.

Study design: Prospective, randomised four-way balanced crossover study.

Methods: Six horses received vonoprazan (0.5 and 1 mg/kg), omeprazole (4 mg/kg) and water (60 mL). Blood samples were collected prior to and up to 72 h post-administration. Plasma vonoprazan concentrations were measured using liquid chromatography-tandem mass spectrometry, and non-compartmental and compartmental pharmacokinetic analyses were performed. Intragastric pH was continuously recorded 12 h before and 24 h after each treatment. The percentage of time pH remained above 4 was compared among treatments.

Results: For 0.5 and 1 mg/kg vonoprazan, respectively, Cmax was 23.7 ± 14.0 and 55.8 ± 18.1 ng/mL (mean ± SD); Tmax was 0.875 (0.25-3.0) and 0.625 (0.08-1.0) h (median and range); and terminal half-life was 6.12 ± 1.65 and 6.29 ± 1.86 h (mean ± SD). At 1 mg/kg, vonoprazan significantly increased the percentage of time pH >4 compared to pre-treatment (91.85% vs. 85.5%; p = 0.007) and placebo (90.28 ± 5.6% vs. 5.68 ± 39%; p = 0.021).

Main limitation: Small sample size which may impact clinical applicability of observed changes and potential variability in pH probe positioning.

Conclusion: Vonoprazan was well tolerated and effectively increased and maintained intragastric pH above 4 at the 1 mg/kg dose in horses.

Keywords: acid blocker; gastric ulcers; horse; novel treatment; pharmacokinetics; vonoprazan.

© 2026 The Author(s). Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.