Two Potential Equine Gastric Ulcer Medications Analyzed

Two Potential Equine Gastric Ulcer Medications Analyzed

Sykes and his team saw a rapid response to the injectable omeprazole, noting that acid suppression occurred within one to two hours for most of the horses.

Photo: iStock

A research team in Australia has been examining equine gastric ulcer syndrome (EGUS) from a different angle than most scientists have in the past, measuring pH levels in two areas of the stomach over time rather than testing gastric fluid from a fasted horse. In doing so, they’ve found that in some horses on certain diets, the duration of acid suppression of oral omeprazole—the current gold-standard for ulcer treatment—could be inadequate for ulcer healing. So, they’re taking the research a step further and considering alternative therapeutic approaches.

Ben Sykes, BSc, BVMS, MS, MBA, Dipl. ACVIM, Dipl. ECEIM, PhD, from The University of Queensland, presented findings from one study and preliminary results from two others at the 2016 British Equine Veterinary Association Congress, held in Birmingham, U.K., in September. In each study he and colleagues used an intragastric pH probe to monitor the acidity of the environment for 23 hours (the 24th hour was used to reset and recalibrate the probe) in the ventral (lower) region of the stomach. In the first study, which appeared in the Equine Veterinary Journal, Sykes and his team revealed that while omeprazole did a great job raising intragastric pH in horses on high-grain/low-fiber diets, it didn’t perform so well in horses on hay-only diets.

They also discovered that under some conditions there was a cumulative effect of dosing—meaning the longer the treatment regimen (measured up to five days), the higher the pH, which is a new finding in the horse. In the end, they determined that using a cookie-cutter dosing recommendation for all horses might not be appropriate, and veterinarians need to consider the diet and management of horses when making dosing recommendations.

“A hay-only diet might be a bad idea in the therapeutic stage, at least in some animals,” he said.

This research got Sykes wondering about other treatment approaches, specifically oral esomeprazole and a long-acting injectable omeprazole formulation.

“In the case of esomeprazole, it’s approximately four times more potent than omeprazole in other species,” he said. “In meta-analysis studies (a statistical approach to combining results from multiple studies), it’s considered the proton pump inhibitor (a class of drugs designed to reduce gastric acid production) of choice in human medicine.”

He conducted a second study looking at effects of dose and diet with two esomeprazole doses (0.5 and 2.0 mg/kg bodyweight per day), and evaluated the percentage of time intragastric pH was over 4 (which is considered a healing range in other species).

“We used the same six horses, and I think that’s important because there’s individual variability in responsiveness, so we can compare apples to apples,” he said. “We found a very similar effect in the high-grain/low-fiber diet, both of the doses were very effective, and even the lower dose was up above the minimum requirement for healing in other species, so that was very encouraging.

“Where it got quite exciting, though, is when we looked at the hay-only diet," he said. "What we saw is that by Day 5 the average observed percentage of time intragastric pH was over 4 was up around 80%. And, in fact, five of the six horses were well above that.”

Sykes said these results are encouraging as they suggest the effects of a hay-only or high-forage diet can be overcome.

“We don’t necessarily need to change our recommendations for how we manage these horses, or their diet, because (feeding a high-fiber diet) is a good thing to do to horses. With the use of esomeprazole we can get good acid suppression, and we can still feed high-fiber diets in the therapeutic phase giving us the best of both worlds,” he said.

“I think as far as oral therapy, esomeprazole has a lot of promise,” he said, acknowledging it warrants further investigation as an alternative to omeprazole for treating EGUS.

In a third study, Sykes looked at the pharmacodynamics of an injectable form of omeprazole. He and colleagues gave a single 20-mL dose intramuscularly and ran the experiment again, this time looking at the percentage of time the gastric pH was higher than 4 over seven days. “We just looked at the hay diet because it’s the more rigid of the two models,” he said.

Sykes and his team saw a very rapid response, noting that acid suppression occurred within one to two hours for most of the horses.

“We had complete acid suppression for a four-day period in all horses, and then between five and seven days, several of the horses still were responding well, some of the horses started to taper off,” he said. “This would support a once weekly dosing regimen.”

Ultimately, this was a pilot study for a once-weekly drug that is still in development, but Sykes noted it “has a lot of promise for overcoming the dietary effects (of a hay-only diet) observed.

“One of the striking things is when you scope these horses (with a gastroscope). With oral omeprazole the squamous ulcers may have healed but the mucosa often still looks a little rough or thickened. In the horses treated with the injectable, the squamous mucosa appears completely normal,” he said. “That was really encouraging.”

In summary, Sykes said the magnitude of acid suppression he saw was consistent with healing in other species. “This warrants clinical investigation and has a lot of promise in terms of overcoming the dietary effects we’ve seen with oral omeprazole,” he said.

Sykes noted in his presentation that he is a consultant to Luoda Pharma, who funded the research.

About the Author

Stephanie L. Church, Editor-in-Chief

Stephanie L. Church, Editor-in-Chief, received a B.A. in Journalism and Equestrian Studies from Averett College in Danville, Virginia. A Pony Club and 4-H graduate, her background is in eventing, and she is schooling her recently retired Thoroughbred racehorse, Happy, toward a career in that discipline. She also enjoys traveling, photography, cycling, and cooking in her free time.

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