Equivalent gain-of-function variants in KCNK3 and KCNK9 and their contribution to distinct TASK K2P channelopathies.

Equine gastric ulcer syndrome (EGUS) is a common condition in horses. Omeprazole, a proton pump inhibitor (PPI) that blocks acid production, is widely used in horses for the treatment of EGUS but it is not universally effective, especially against glandular disease., Potassium‐competitive acid blockers (P‐CABs) are an alternative class of drugs used to treat gastric disorders in human medicine. Potassium‐competitive acid blockers and PPIs both work by reducing the amount of acid produced in the stomach, but they do so via different mechanisms. Proton pump inhibitors work by inhibiting hydrogen ion secretion by the H+/K+ ATPase proton pump in the parietal cells of the stomach, which is responsible for secreting acid. Potassium‐competitive acid blockers work similarly by selectively inhibiting the influx of potassium ions via the H+/K+ ATPase proton pump, thus preventing the exchange of hydrogen ions., A key advantage of P‐CABs in human medicine is that their absorption is not affected by food. This is a limitation of PPIs, namely omeprazole in horses, wherein an unnatural overnight fasting period must be imposed upon the horse to optimise absorption and therefore acid suppression., This imposed fasting has significant deleterious welfare implications in many horses. A further advantage of P‐CABs is a more rapid onset of effect, compared to PPIs, as, unlike PPIs, they are not prodrugs and do not require activation by acid., As such, they provide more rapid symptomatic relief from disease. Potassium‐competitive acid blockers might also be effective for patients who do not respond well to PPIs as they have a longer duration of acid suppression than PPIs., This is especially relevant in horses where omeprazole has a short duration of action compared to other species, which is likely a significant contributory factor to their less than complete efficacy. In the current study, it was hypothesised that vonoprazan would be more effective than omeprazole in the suppression of acid production. To that end, the objectives of this study were (1) to describe the plasma pharmacokinetics of vonoprazan following a single oral administration of 0.5 and 1 mg/kg to horses and (2) to describe the pharmacodynamics of vonoprazan following a single oral administration of the same doses compared to a single 4 mg/kg dose of oral omeprazole.