Omeprazole and equine gastric ulceration

Equine Gastric Ulcer Syndrome (EGUS) is a common condition of the horse, affecting a broad range of horse usages and types. Recently the terminology of the syndrome has been expanded to include terms Equine Squamous Gastric Disease (ESGD) and Equine Glandular Gastric Disease (EGGD) to describe diseases of the squamous and glandular mucosa of the stomach, respectively. Omeprazole, a proton pump inhibitor that blocks acid production, is considered the treatment of choice for EGUS, yet little is known about the factors that affects its efficacy, such as the impact of formulation, diet and dose. Further, although it is commonly believed that the once daily administration of omeprazole results in durations of acid suppression exceeding 24 hours, there is conflict in the literature as to the validity of this belief. Recent clinical studies have demonstrated that the healing rate for EGGD is inferior to that of ESGD, raising further questions as to the efficacy of omeprazole under clinically relevant conditions. One potential reason for this observation is that the duration of intra-day acid suppression required for healing of ESGD may be less than that for EGGD. This, coupled with the possibility that once daily administration of omeprazole may not result in acid suppression for the entire 24 hour treatment interval, provides a potential explanation for the poor EGGD healing rates that have been recently reported. We investigated the factors that affect the efficacy of omeprazole in the horse: (1) The effect of formulation and diet on the pharmacokinetics of omeprazole (2) We developed a model that permitted continuous intra-gastric pH measurement under clinically relevant conditions; (3) The impact of diet and dose on the pharmacokinetics and pharmacodynamics of omeprazole were investigated. We found that physical protection was necessary to protect the omeprazole from degradation in the acidic environment of the stomach and to improve bioavailability, although there were minimal differences between the different types of protection available (i.e. enteric coated granules vs. buffering). The studies suggested that both diet and dose impact on the pharmacodynamics of omeprazole in the horse, but there was a low overall efficacy of omeprazole under the ad libitum roughage dietary conditions, which was surprising but potentially significant. A wide degree of inter-individual variation was present is bioavailability. Importantly, key pharmacokinetic and pharmacodynamic parameters correlated poorly, which suggested that plasma concentrations are poorly predictive of pharmacodynamic response in the horse. These findings may suggest why poor healing rates are reported for EGGD.