576


NOVEMBER 2022


a)


10 12


2 4 6 8


0 Day 0 Day 14 0 12 3 4 Day 28


18 20 b)


10 12 14 16


0 2 4 6 8


Day 0


Day 14 01 2


Day 28


Fig 1: Number of horses per grade of ESGD (a) and EGGD (b) lesions per timepoint. ESGD grading was performed on a 0–4 scale, EGGD grades on a 0–2 scale. Note: absent grades at a timepoint indicate lack of individuals having that grade at that timepoint


annual multivalent vaccine (Merck Animal Health) in the opposite side of neck on the same day of the fourth dose, and this is recognised to be a limitation of the study when evaluating injection site reactions (Supplementary Item 1). Physical examinations and bloodwork performed prior to


the study revealed no significant findings. Refer to Table 2 for statistically significant changes in CBC and SBP values. Many values showed significant differences but maintained within the normal reference range. Mean haematocrit (HCT) stayed within normal range from baseline at 47.71% (95% CI 45.85%–49.58%) to Day 28 check at 37.70% (95% CI 35.51%– 39.88%). This drop of nearly 10% was considered significant (p < 0.0001). Bodyweights were significantly lower (mean change


20.1  12.9 kg) on Day 28 when compared with baseline (p < 0.0001). This was a decrease of 3.8% bodyweight from


baseline (Day 2) to study Day 28.


Pharmacokinetic analysis The Cmax ranged from 21.9 ng/ml to 65 ng/ml with a mean of


46.2 ng/ml ( 17.4 ng/ml) and the Tmax for all horses occurred at six hours following injection. The calculated AUC ranged from 933.7 ng/ml*h to 2732 ng/ml*h. A box and whisker plot of omeprazole concentrations per time point can be seen in Figure 4.


In order to identify the long-acting concentrations of


omeprazole demonstrated after LAO-USA dosing, mean PK values were evaluated up to 7 days following dosing (Fig 5). These values are demonstrated after 48 h of receiving the dose so as to represent sustained levels provided by the formulation after the Cmax had been reached. The mean omeprazole concentration across all horses from 48 to 168 h


was 9.6 ng/ml (SD  4.6). All horses maintained omeprazole concentrations above 4.3 ng/ml up to 168 h following dosing.


Discussion Clinical efficacy Previous studies evaluating efficacy of omeprazole formulations in the treatment of EGUS include complete lesion healing as a measurable outcome. The 35% ESGD healing rate of the current formulation is significantly lower than the previously reported 100% healing with the other currently studied LAO formulation (Rendle et al., 2018b; Sykes et al., 2017a). ESGD scores significantly decreased by greater than one grade in 74% of horses in this study, with the mean improvement in ESGD scores of 1.41 grades. This improvement rate is lower than previously reported where improvement by at least one grade was reported in all horses using a similar grading scale with the alternative LAO


Injection site reaction grading following repeated doses


25 20


10 15


5 0 Injection 1 Injection 2 Injection 3 Grade 0 Grade 1 Grade 2 Grade 3


Fig 2: Number of horses having injection site reactions after each injection, represented by grade of reaction. Injection site reactions lasted from 1 to 4 days per horse. The documented grades reflect the highest grade each horse received during the dose period


© 2021 EVJ Ltd Injection 4


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