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1 mg/kg bwt per os s.i.d. was equally effective as Gastrogard1 at 4 mg/kg bwt per os s.i.d. in a recent clinical trial, despite an only modest increase in bioavailability (Birkmann et al. 2014). Considering this, the authors’ consider that the use of lower doses of buffered formulations warrants further investigation and the authors routinely use 2 mg/kg bwt per os s.i.d. as a treatment dose when using buffered formulations. In a study using another buffered formulation, a reduction below this dose to 1.6 mg/kg bwt was associated with a decreased response rate (Sykes et al. 2014c) and, as such, a reduction below 2 mg/kg per os s.i.d. is not recommended. In the authors’ opinion, a reduction in the dose of plain omeprazole below the label dose of 4 mg/kg bwt is not recommended until the relative pharmacokinetics of this formulation are further defined. Based on experimental studies (Andrews and Jenkins 1992;
Jenkins et al. 1992a, b; Daurio et al. 1999; Haven et al. 1999; Sandin et al. 1999; Andrews et al. 2006), it is widely believed that once daily administration of omeprazole results in 24 h of acid suppression. However, the methodology used to measure gastric acidity in those studies may not be truly reflective of mucosal pH (Merritt et al. 2003). A study using pH probes inserted in ponies with an indwelling gastric cannula, which the authors believe offers the most reliable model of intra-gastric pH measurement, has suggested that the duration of acid suppression following dosing at 4 mg/kg bwt may be as short as 12 h (Merritt et al. 2003). Considering this, the timing of administration may be important with exercise considered to be the peak risk period for ESGUS development (Lorenzo- Figueras and Merritt 2002). A recent study in Thoroughbred racehorses found no clear advantage of administration of omeprazole 1–4 h prior to exercise compared with administration post exercise but the results suggested that an effect may be present and that a small, no cost management change may improve efficacy (Sykes et al. 2014d). Regardless of the formulation or dose used it is important to
recognise that at best only approximately 80% of animals will heal within a 28 days treatment period (Murray et al. 1997; Andrews et al. 1999b; Doucet et al. 2003; Sykes et al. 2014d). As such, repeat gastroscopy is recommended prior to the cessation of therapy to ensure that healing has occurred. The factors contributing to nonresponders are poorly described but potentially include the failure to reduce associated risk factors and individual variation in the absorption of omeprazole. It has recently been reported that a wide range of interindividual variation is present in the oral bioavailability of omeprazole with 3/12 horses in one study being poor absorbers regardless of the conditions studied (Sykes et al. 2014e). As such, it is tempting to speculate that the animals that fail to respond to conventional dose omeprazole therapy may simply be poor absorbers of the drug and the authors consider the presence of severe, persistent ESGUS at follow-up examinations to be highly suggestive of a failure of omeprazole to achieve acid suppression in that animal. Under such conditions (i.e. in individuals that appear refractory to treatment with omeprazole) alternative therapeutic agents should be considered. Avariety of other drugs have been used in the treatment of
ESGUS, most commonly the H2 receptor antagonists ranitidine and cimetidine. Both drugs work via competitively blocking the H2 receptor on the parietal cell and their efficacy is dependent on maintaining plasma concentrations. Ranitidine, most commonly used at 6.6 mg/kg bwt per os t.i.d., has been
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shown to effectively suppress gastric acidity in experimental studies (Campbell-Thompson and Merritt 1987; Sangiah et al. 1988; Murray and Grodinsky 1992; Murray and Schusser 1993) and provides an option for acid suppressor therapy where omeprazole is not available or ineffective as discussed above. Cimetidine is relatively poorly studied and its use is not justified in the authors’ opinion. Nonpharmaceutical methods, such as feed supplements
and antacids, of treating ESGUS are popular amongst owners, typically because of low cost and availability. Although antacids can effectively reduce gastric acidity, their effect is short-lived (≤2 h) (Murray and Grodinsky 1992; Clark et al. 1996) and, as such, their use beyond short termsymptomatic control is not recommended. Mucosal protectants, such as pectin- lecithin complexes, may play a role in providing a physical barrier between the mucosa and acid, and symptomatic relief with their use is often reported anecdotally. To date their efficacy as a therapeutic agent is unproven with 2 studies failing to demonstrate a protective effect in a fasting model of ESGUS (Murray and Grady 2002; Sanz et al. 2014) despite initially promising results in clinical patients (Venner and Lauffs 1999). Whether the fed/fasted model often used to study such products is representative of the clinical setting is, in the authors’ opinion, disputable and studies in clinical patients may yield more relevant results. Recently, it has been demonstrated in a clinical study that a feed supplement consisting of salts of organic acids (SOC) in combination with B vitamins may be beneficial in the treatment of ESGUS (Hellings and Larsen 2014) and the authors believe that further investigation of neutraceuticals under clinical conditions is warranted.
Prevention
The approach to prevention of ESGUS is similar to treatment. In many cases a significant reduction in risk factors is not possible and the risk of recurrence is typically moderate to high. Prevention should be approached on a case by case basis, wherein the greater the ability to impact on risk factors, the lower the need for additional therapy. Although ineffective in feed deprivation models (Murray and Grady 2002; Sanz et al. 2014), the use of mucosal protectants such as the pectin- lecithin complexes may be adequate in low–moderate risk environments, especially when used in combination with antacids where they have been shown to be beneficial (Sykes et al. 2013). In contrast, a formulation containing sea- buckthorn berries failed to demonstrate a protective effect for ESGUS in a fed/fasted model (Huff et al. 2012) although, as previously mentioned, the authors question the validity of this model. Omeprazole is indicated in cases where the risk of recurrence is deemed to be high. It is typically used at 1.0 mg/kg bwt per os s.i.d. using buffered formulations (McClure et al. 2005b; Endo et al. 2012), although 0.5 mg/kg bwt per os s.i.d. of an enteric-coated formulation (Gastrozol)2 has recently been shown to be as effective under specific conditions (Sykes et al. 2014a).
Summary
The risk of ESGUS increases with increased intensity of management with a high prevalence of animals potentially affected in high risk populations. Risk factors are well described and the ability to reduce exposure to risk factors, where possible, should reduce the risk of disease. However, ESGUS
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