Vonoprazan pharmacokinetics and effects on gastric pH following administration to fed and fasted horses
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: 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…
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