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NOVEMBER 2022
Other long-acting omeprazole (LAO) intramuscular (IM)
compounded formulations are currently being studied (LAO- UK and LAO-AUS) (Rendle et al., 2018a,b; Sykes et al., 2017a) and are not currently available in the United States. The current formulation (LAO-USA: Omeprazole BioRelease: BET Pharmacy) utilises a novel extended-release system and, similar to other LAO formulations, has the potential to deliver slow-release concentrations of drug while bypassing parenteral bioavailability concerns. The LAO-USA suspension contains 2.5 grams omeprazole compounded in a long- acting vehicle. This aim of the study was twofold: A) To determine clinical
efficacy and safety of the LAO-USA formulation in performance horses with naturally occurring ESGD and EGGD over a 28-day period and B) to evaluate pharmacokinetics of this formulation over a seven-day period. We hypothesised that this formulation would improve ESGD and EGGD scores in the performance horse by Day 28 following weekly IM administration. We hypothesised that the current formulation would not have significant side effects on biochemical parameters and would only elicit mild injection site reactions following dosage. We also hypothesised that LAO-USA would provide consistent serum concentrations of omeprazole for up to 7 days.
Materials and methods Horses
Twenty-three horses participated in the efficacy and safety portion of this pilot clinical trial study, and six of 23 were randomly selected for the pharmacokinetic analysis portion of the study. Thirteen mares and ten geldings were included in the study and breeds included Thoroughbred, Warmblood and Quarter Horse. The age range was 5–20 years (median 12 years, range 5–20 years), and weight range of horses enrolled in the study was 425–638 kg. All horses participating in the study were active with the university equestrian programme or the competitive university polo programme. The general exercise regime included moderate intensity riding in English, Western and Polo disciplines approximately 3–4 times per week. The horses had an increase in workload from one week prior to the study to five weeks after the study, correlating with the undergraduate student competitions and academic schedule. All horses were housed at the same location and received ad libitum grass hay diets with free choice access to water. Horses were group housed in large paddocks including run-in shelters with no more than eight horses per paddock. All horses were kept on their regular vaccination, dental prophylaxis and osteoarthritis management schedules and received this care during the study. Refer to Supplementary Item 1 for veterinary maintenance schedule. Physical examination, bodyweight, complete blood count and biochemistry profile (CBC/SBP) were performed on all
horses 2 days prior to the beginning of the study (Day 2) to monitor for presence of concomitant medical conditions and to establish baseline data prior to drug administration. Bodyweights were taken on a standard scale [Tru-TestTM Model 700: Tru-Test Limited]. Blood analyses were performed by the University Clinical Pathology Laboratory using standard protocols (Siemens Advia 120 Hematology Analyser; Roche Cobas 501 Biochemistry Analyser). These measures were repeated following the last dose at Day 28 of the study to
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monitor for any change that occurred over the course of the study period.
Drug administration Injection of LAO-USA was performed in all 23 horses every 7 days for four injections. Formulations were reconstituted at room temperature according to package directions including shaking the formulation for 45 seconds following addition of diluent. A 5 mg/kg dose was drawn up for each horse. Injections were given with the recommended
18 gauge 9 1 1/2” needle IM in alternating sides of the neck: first and third injections were given on the left side, while second and fourth were administered on the right side. Following each dose, injection sites were monitored daily and grades were recorded to provide an additional safety measurement of drug administration. The grading scale for injection site reactions was from zero to three, with zero being no inflammation and three being severe inflammation at the injection site. Refer to Table 1 for a detailed description of injection site reaction grading scale.
determine enrolment in the study, then again at Days 14 and 28. A standard 3-m gastroscope [Teleview: Advanced Monitors Corp.] was used. Each horse was fasted from food approximately 24 h prior to gastroscopy with free access to water. Horses were restrained in standard stocks for gastroscopy and given detomidine [Dormosedan: Zoetis USA] (0.03 mg/kg i.v.) to facilitate each gastroscopy. A dental speculum was placed and slightly opened to prevent damage to the gastroscope during procedure. Both the
Gastroscopy A total of 30 horses underwent gastroscopy prior to the study, of which 23 met the inclusion criteria of ESGD grade ≥2/4 and/or EGGD grade ≥1/2. Gastroscopic scoring of ESGD and EGGD was evaluated using a previously described scoring system (Sykes et al., 2015b, 2017c). A grading system of 0-4 was used to evaluate ESGD lesions; zero being no evidence of squamous ulceration and four being severe squamous ulceration (Sykes et al., 2015b, 2017c). Glandular mucosa was graded as follows: grade 0/2 indicates a normal mucosal surface with no gross evidence of loss of mucosal integrity; grade 1/2 indicates the presence of mild to moderate lesion (s) with evidence of loss of mucosal integrity; and grade 2/2 indicates the presence of severe lesion(s) with evidence of loss of mucosal integrity (Sykes et al., 2017c). Mild hyperaemia of the glandular mucosa without visible loss of mucosal integrity was not considered clinically significant. Lesion improvement was noted as a decrease in lesion grade by at least 0.5 grade, and lesion healing was an additional outcome considered and was defined as a lesion score of “0” from a baseline higher grade following treatment as previously described (Sykes et al., 2017a). Gastroscopy was performed on study Days 2to
TABLE 1: Injection site reaction grading scale Grade Description
0No inflammation 1
Mild inflammation: oedema only
2 Moderate inflammation: oedema, heat and pain 3
Severe inflammation: oedema, heat, pain and systemic signs
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