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a dose escalating strategy to achieve this outcome. After assessment of the diet, ideally including an overnight fast to maximise drug absorption, an initial dose is selected, typically 1 or 2 mg/kg bwt by mouth once per day for an enteric coated or buffered formulation, respectively, treatment is initiated and the response to treatment followed. For horses with clinical signs, a change is expected within 7 days while animals with gastroscopically diagnosed disease should be reassessed at 3 weeks. If clinical signs persist beyond 7 days, or ESGD lesions are still present at 3 weeks, then the dose is doubled and the monitoring continued.
Drug interactions The potential for drug interactions, specifically sucralfate, to affect the absorption of omeprazole in the horse has previously been highlighted (Sykes et al. 2015a). As discussed above, the role of sucralfate in the management of EGGD is likely less important than previously believed as it appears, based on pilot data, that good rates of EGGD healing can be achieved with acid suppression alone when an appropriate magnitude and duration of suppression is achieved (Sykes et al. 2017a). However, anecdotally, sucralfate may still be advantageous in the management of clinical signs, especially in the early stages of treatment, and insufficient evidence is presently available to completely discount its potential utility as an adjunctive agent in treatment. If it is to be administered, it should not be administered concurrently with omeprazole. Instead, a minimum of 60–90 min following omeprazole administration should be allowed before sucralfate administration to ensure absorption of the majority of the oral omeprazole dose before any potential interaction may occur. In practice, the author recommends administration of sucralfate at the same time as morning and evening feeding.
Novel alternatives to oral omeprazole
Oral omeprazole has been a cornerstone of EGUS treatment for nearly 20 years. However, as discussed above, some patients demonstrate an inadequate response to current treatment regimens, in particular patients with EGGD. Equally, the use of an oral medication is not possible in some patients such as refluxing or dysphagic patients that cannot tolerate oral medications, or animals with delayed gastric emptying, where the increased dwell time of omeprazole in the stomach is likely to result in increased acid degradation and thus reduced efficacy. Given these factors, recent research has focused on alternative PPI therapy for the horse. Specifically, esomeprazole (both oral and i.v.) and a novel, long-acting, injectable formulation of omeprazole have recently been reported and warrant discussion for the management of cases where traditional oral omeprazole therapy is ineffective or inappropriate.
Esomeprazole In humans, esomeprazole, the S-enantiomer of omeprazole, is considered the PPI of choice with two meta-analysis studies demonstrating its superiority over other PPIs in treating clinical disease (Edwards et al. 2006; Gralnek et al. 2006). When compared with omeprazole in humans, it has a superior pharmacokinetic profile attaining a higher area-under-the curve (AUC), longer duration of action and higher intragastric pH with less interindividual variability observed (Johnson 2003;
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Shin and Sachs 2008). Although the pharmacokinetics of oral esomeprazole have not been described in the horse, the pharmacodynamics of a novel, enteric coated formulation of esomeprazole has recently been described (Sykes et al. 2017d). When administered to horses following the withholding of feed overnight, the magnitude and duration of acid suppression observed following the administration of 0.5 and 2.0 mg/kg bwt by mouth once daily was comparable to that achieved in the same horses receiving 1.0 and 4.0 mg/kg bwt by mouth once daily, respectively, of commercial, buffered omeprazole paste (Sykes et al. 2017b, d). However, when administered to horses consuming ad libitum roughage at a dose a 2.0 mg/kg bwt by mouth once daily a more pronounced and consistent acid suppressive response was observed with esomeprazole when compared with the administration of 4.0 mg/kg bwt by mouth once daily of commercial, buffered omeprazole paste in the same horses under the same conditions (Sykes et al. 2017b,d). Specifically, on Day 5 the therapeutic threshold for healing, as reported in other species, was exceeded in 5/6 horses on esomeprazole at 2.0 mg/kg bwt by mouth once daily paste (Sykes et al. 2017d) compared with 3/6 horses on omeprazole at 4.0 mg/kg bwt by mouth once daily (Sykes et al. 2017b). These findings suggest that oral, enteric coated esomeprazole may be advantageous in some horses consuming ad libitum roughage diets. The pharmacodynamics of i.v. esomeprazole has also
been described following the administration of 0.5 mg/kg bwt i.v. once daily over a 14-day period (Videla et al. 2011). On Days 5 and 14, gastric juice pH was higher in esomeprazole treated horses than saline treated controls. The authors concluded that i.v. esomeprazole shows promise for treatment of horses with conditions that restrict oral intake of omeprazole paste (Videla et al. 2011).
Parenteral administration of omeprazole The use of i.m. omeprazole, using a traditional formulation, has previously been described and i.m. dosing was more effective than oral administration at the equimolar dose (Sandin et al. 1999). However, traditional formulations of omeprazole are unstable once reconstituted, while their highly alkaline nature is potentially irritant (Jenkins et al. 1992), which reduces their clinical usefulness. Intravenous administration of a traditional formulation of omeprazole has also been described (Andrews et al. 2006). Although a pronounced and consistent acid suppressive effect was observed one hour after administration on Day 5, the magnitude of acid suppression measured one hour after administration on Day 1 was marginal, and the effect observed at this time point was inconsistent and highly variable (Andrews et al. 2006). Similarly, although the mean magnitude of acid suppression following the 4th dose, as measured one hour prior to administration of the 5th dose on Day 5, was above the therapeutic threshold, the duration of acid suppression also appeared highly variable and inconsistent (Andrews et al. 2006). A potential explanation for the delayed, and highly variable, response observed following i.v. administration of traditional formulations is that omeprazole has a very short half- life following i.v. administration in the horse (approximately 30 min) (Jenkins et al. 1992; Sykes et al. 2015d). This makes traditional formulations pharmacokinetically unsuitable for parenteral administration as serum concentrations are only present for a limited duration within each 24-h treatment interval.
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