Vonoprazan pharmacokinetics and effects on gastric pH following administration to fed and fasted horses.
Abstract: 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. Objective: 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. Methods: 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, C was 23.7 ± 14.0 and 55.8 ± 18.1 ng/mL (mean ± SD); T 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). Conclusions: Small sample size which may impact clinical applicability of observed changes and potential variability in pH probe positioning. Conclusions: Vonoprazan was well tolerated and effectively increased and maintained intragastric pH above 4 at the 1 mg/kg dose in horses.
© 2026 The Author(s). Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
Publication Date: 2026-01-14 PubMed ID: 41532453DOI: 10.1111/evj.70128Google Scholar: Lookup
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Summary
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Research Overview
- This study investigated how vonoprazan, a new type of acid suppressant, behaves in the body of horses and how it affects stomach acidity when given in fed and fasted states.
- The researchers aimed to understand if vonoprazan could effectively increase stomach pH, potentially offering a better treatment option for equine gastric ulcer syndrome compared to existing drugs like omeprazole.
Background and Rationale
- Equine gastric ulcer syndrome (EGUS) is a common condition in horses characterized by ulcers in the stomach lining.
- Current treatments primarily use proton pump inhibitors (PPIs) such as omeprazole, which require administration on an empty stomach to be effective.
- Potassium-competitive acid blockers (P-CABs), like vonoprazan, are newer acid-suppressing agents that, in humans, offer advantages such as rapid action and less sensitivity to food intake.
- This study hypothesized that vonoprazan would follow linear pharmcokinetics in horses and effectively increase gastric pH levels.
Study Design and Methods
- Type: Prospective, randomized four-way balanced crossover study involving six horses.
- Treatments administered included:
- Vonoprazan at dosages of 0.5 mg/kg and 1 mg/kg orally
- Omeprazole at 4 mg/kg orally (standard PPI comparator)
- Water (60 mL) as placebo control
- Blood samples collected before treatment and up to 72 hours post-administration to measure plasma vonoprazan concentrations.
- Vonoprazan levels measured by liquid chromatography-tandem mass spectrometry.
- Pharmacokinetic analysis involved both non-compartmental and compartmental methods to interpret drug absorption, distribution, metabolism, and elimination.
- Intragastric pH was continuously monitored using probes, recording for 12 hours before and 24 hours after each treatment.
- Primary outcome was the percentage of time the gastric pH remained above 4, a threshold considered therapeutic for ulcer healing.
Key Findings
- Pharmacokinetics:
- Plasma concentration peaks (C_max) for vonoprazan were approximately 23.7 ng/mL at 0.5 mg/kg and 55.8 ng/mL at 1 mg/kg doses.
- Time to peak concentration (T_max) was rapid, ranging from 0.08 to 3 hours, typically under 1 hour.
- Terminal half-life for vonoprazan was about 6 hours across both dosages, indicating how long the drug stays active in the system.
- These results support linear kinetics across the doses studied.
- Effect on Gastric pH:
- The 1 mg/kg vonoprazan dose significantly increased the percentage of time the gastric pH remained above 4, reaching about 91.85% post-treatment compared to 85.5% pre-treatment.
- The same dose showed a statistically significant increase compared to placebo control (90.28% vs. 5.68%).
- Omeprazole was used as a comparator but specific comparative efficacy data to vonoprazan is not detailed in the abstract.
Conclusions and Clinical Implications
- Vonoprazan was well tolerated by horses at the doses tested with no reported adverse events.
- It effectively and consistently maintained intragastric pH above the therapeutic threshold, especially at 1 mg/kg.
- The rapid onset and sustained pH elevation suggest potential advantages over PPIs that require fasting conditions.
- Limitations include a small sample size, which may affect the generalizability of results to the wider horse population.
- Potential variability in pH probe positioning could influence pH measurement accuracy.
- Overall, vonoprazan shows promise as a novel, effective treatment for EGUS, warranting further research in broader clinical trials.
Cite This Article
APA
Morales CJ, Sykes BW, McKemie DS, Kass PH, Knych HK.
(2026).
Vonoprazan pharmacokinetics and effects on gastric pH following administration to fed and fasted horses.
Equine Vet J.
https://doi.org/10.1111/evj.70128 Publication
Researcher Affiliations
- K. L. Maddy Equine Analytical Chemistry Laboratory (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- BW Sykes Consultancy, Coffs Harbour, New South Wales, Australia.
- K. L. Maddy Equine Analytical Chemistry Laboratory (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- K. L. Maddy Equine Analytical Chemistry Laboratory (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Grant Funding
- UC Davis Center for Equine Health
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