To date, there have been no generic products that have the efficacy of Gastroguard or Ulcerguard paste formulations in managing gastric ulcer disease in horses, and in particular equine squamous gastric disease (ESGD). Compounded formulations have achieved poor bioavailability.
A recent Australian study has examined the pharmacokinetic and pharmacodynamic effects of a novel in-feed, enteric-coated dry granule preparation compared to the currently available enteric-coated oral omeprazole paste [Wise, J.C.; Hughes, K.J.; Edwards, S.; et al. Pharmacokinetic and pharmacodynamic effects of 2 registered omeprazole preparations and varying dose rates in horses. J Vet Intern Med Nov 2020; DOI: 10.1111/jvim.15971].
For the horses in the study, feed was withheld for 10 hours prior to dosing with either oral omeprazole product at a dosage based on body weight. Three different omeprazole formulations were used with three horses in each group—all horses received all of these treatments with at least five days of washout between each treatment:
- Intravenous omeprazole
- An existing enteric-coated oral paste
- A novel in-feed enteric-coated dry granule preparation mixed in bran, consumed within 2-5 minutes
The study looked at several parameters: a) bioavailability of oral absorption of oral products; b) dose titration of novel granules at two different doses; and c) pharmacodynamic comparisons.
Regarding bioavailability, plasma concentrations of omeprazole were measured before treatment and at 1, 5, 10, 15, 30, 45, 60, 75, 90, 105, 120 and 150 minutes and at 3, 4, 5, 6, 8, 12 and 24 hours following omeprazole treatment.
For the dose titration study comparing 2 mg/kg and 4 mg/kg of the novel granule formulation, gastroscopy and 24-hour measurement of gastric pH were obtained.
Comparative pharmacodynamics between the paste and oral formulations were assessed using plasma concentrations at many time points prior to treatment, after the first treatment, and on Day 5.
In addition, gastric squamous ulcer scores and 24-hour gastric pH were analyzed on treatment Days 1 and 6.
Results were as follows:
- Maximum plasma concentration occurred between 15-45 minutes for the novel granular form and between 30-90 minutes for the paste.
- The novel granular form elicited increased gastric pH in the 24-hour period after a single treatment and was associated with a lower percentage of time when gastric pH <4. No differences were seen between the 2 mg/kg and 4 mg/kg dose. Untreated horses had gastric pH <4 for most of a 24-hour sampling period.
- Repeated oral daily dosing of the novel granules at 2 mg/kg and paste at 1 mg/kg had comparable effects on gastric fluid—increased pH 24 hours after treatment and less percentage of time with pH <4.
- The novel granule and oral paste forms had similar effects, and neither elevated pH of gastric fluid with repeated administration of either produce.
- Repeated daily administration of both oral products resulted in reduced gastric squamous ulcer scores on Day 6 in comparison to Day 1 and compared to untreated horses. Glandular mucosa was not evaluated.
- Plasma concentrations of both oral products were similar and experienced similar rapid absorption and elimination (mean half-life of 60 minutes). After repeated daily administration, maximal plasma concentration of the novel granule began earlier and at higher levels than the paste, but ended sooner than plasma concentrations of the paste.
- Bioavailability of the novel granule was 50%; bioavailability of the paste was 30%.
Based on these findings, it is thought that the novel granule formulation might be a reasonable alternative to omeprazole paste, especially when only a small amount of bran (or appropriate feed) is offered to accommodate fasting overnight, then medication administration an hour before feeding a full meal.
Both oral products exerted similar benefits of increased gastric pH compared to untreated horses.