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Fig 5: Sustained levels of omeprazole following dosing of LAO- USA. Mean serum omeprazole concentrations represented after Cmax, from 48 to 168 h following initial dose
2018b). These results support the current recommendation for LAO formulations to evaluate lesion improvement after 2 weeks dosing and continuing for another 2 weeks if lesion grading has not improved (Rendle et al., 2018a,b). It is recognised that a small sample size (n = 6) had
EGGD, and the proportion of horses in this study with baseline EGGD (26%) is consistent with previous prevalence reports of EGGD in performance horses (Andrews et al., 1999; Husted et al., 2010; Nieto et al., 2004; Sykes et al., 2015a). Healing rates of EGGD are challenging to interpret in light of the fact that no significant change in EGGD scoring was demonstrated in this study. In a previous study of a different LAO formulation, a larger population of horses with EGGD was studied and showed 81% and 100% lesion healing following 4 weeks of treatment (Rendle et al., 2018b; Sykes et al., 2017a; respectively). This report and others have theorised that the mechanism of EGGD healing may be related to acid suppression, but further studies would be needed to characterise the mechanism of EGGD healing that occurred (Sykes, 2019; Sykes et al., 2017a). A previous study utilised different formulations and subtle differences in feeding and exercise regimes which may also account for differences in EGGD healing. The pathogenesis and aetiology of EGGD development is known to be complex and carries a high degree of interindividual variability which may account for the variation in EGGD healing results seen in this study compared to previous results (Rendle et al., 2018a; Sykes et al., 2017a; Varley et al., 2019).
Safety In the current study, the rate of injection reactions following the first two doses was 8% and 13%, respectively, while it increased to 22% and 48% following the last two doses. A recent consensus statement for the treatment of EGGD suggests that with IM LAO formulations, rotating injection sites
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and/or utilising the gluteal muscles may be useful in reducing injection site reactions (Rendle et al., 2018a). It is possible that since each side of the neck received two injections of drug, the neck may have been sensitised to the drug and thus had an exaggerated reaction than if the injection was given in a novel area. In a previous study with IM LAO, one injection site reaction was reported and described as mild swelling at the injection site 12 to 24 h following administration (Sykes et al., 2017a). The volume of injection per dose in the current study was approximately 5 mL per injection, while in the previous study the volume of injection was 20 mL per injection (Sykes et al., 2017a). It is clear that the two formulations are different in volume and vehicle; therefore, comparison of injection site reactions between the two is difficult. Other reactions reported with LAO include transient, nonpainful swellings in less than 10% of horses and nonpainful reactions in 5% of horses (Rendle et al., 2018a,b). It is recognised that a different formulation was used in the current study; therefore, further investigation would be warranted to determine whether the long-acting vehicle in the current formulation was associated with more injection site reactions. In the current study, it is recognised that although medications were reconstituted and administered at room temperature, outside ambient temperatures in the area at the time of study were low
(ranging from approximately 17°Cto5°C). It is unknown what effects the ambient temperature may have on injection reactions and this warrants further study. Although there were statistically significant clinicopathologic
changes, these may have been influenced by nonfasted sampling prestudy compared to fasted sampling at the completion of the study. This oversight is recognised as a limitation in data interpretation. Many of the significant differences in SBP values are consistent with fasting changes. The decrease in HCT was not associated with anaemia and remained within the reference range before and after the study. One toxicological study followed high doses of oral omeprazole for 21 days and measured haematological values following treatment with no clinically significant changes to haematological parameters (European, 2002). In addition, dosing with LAO at accepted doses revealed no clinically significant changes in haematological parameters (Di Salvo et al., 2016). As the current study haematological findings correlate with previous findings, we provide further evidence to support systemic safety for this formulation, though it is recognised that local reactions were common. Decrease in bodyweights likely was associated with
change in workload of all horses during the study. All horses were used by students for on-site training/competitions during the study period. The lack of control over this exercise variable is considered a limitation in this study, and further study may be necessary to determine effects on bodyweight. The authors do not consider the decrease in bodyweights to be an adverse side effect of the drug administration in the current study, but rather the result of an increase in conditioning programme with the university schedule.
Pharmacokinetic analysis Previous pharmacokinetic studies following both oral and parenteral omeprazole dosing are reported (Daurio et al., 1999; Di Salvo et al., 2016; Jenkins et al., 1992; Sykes et al., 2015b, 2017a,b,c). However, these reported values are difficult to extrapolate to a different formulation given by a different route and given the fact that therapeutic
[Omeprazole]serum (ng/ml)
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