EQUINE VETERINARY EDUCATION Equine vet. Educ. (2022) 34 (11) 573-580 doi: 10.1111/eve.13546
Original Article
Clinical efficacy, safety and pharmacokinetics of a novel long-acting intramuscular omeprazole in performance horses with gastric ulcers
M. L. Lehman , L. Bass , D. L. Gustafson, S. Rao and E. S. O’Fallon
Department of Clinical Sciences, Colorado State University College of Veterinary Medicine and Biomedical Sciences, Fort Collins, Colorado, USA *Corresponding author email:
lehmandvm@gmail.com
Keywords: horse; squamous; glandular; omeprazole; long-acting injectable
Summary Oral omeprazole is used in the management of equine gastric ulcer syndrome (EGUS). However, its use may have limitations with regard to individual variation in absorption and the impact of dietary management on bioavailability. The objective of this study was to determine whether a novel compounded long- acting injectable omeprazole (LAO-USA) formulation would provide consistent serum omeprazole concentrations and to determine whether it was clinically safe and efficacious in the reduction of EGUS. Twenty-three horses with EGUS described as having evidence of equine squamous gastric disease (ESGD) and/or equine glandular gastric disease (EGGD) received a 5 mg/kg bwt intramuscular injection of LAO-USA once every 7 days for four doses. Gastroscopy was performed prior to the study and at Days 14 and 28. Pharmacokinetic analysis was performed to determine omeprazole concentrations over 7 days. Safety was measured by monitoring injection site reactions daily and bloodwork screening prior to and following the study. Of the horses with ESGD, 78% had improvement by Day 14 (p = 0.0035), with no further improvement from Day 14 to 28 (p > 0.99). ESGD grades from Day 0 to 28 decreased
significantly (95% CI 1.92 to 0.91 grades) (p = 0.0002). Out of the horses (6/23) that had glandular lesions, 5/6 healed over time; however, this was not a significant change (p = 0.75). Injection reactions included oedema, heat and pain at the injection site. Considering the total number of injections across the whole study, 23% of horses experienced an injection site reaction. The number of injection site reactions increased following each dose (8%, 13%, 22% and 48%, respectively). The formulation did not appear to have adverse systemic effects.
Serum omeprazole mean Cmax was 46.2 ng/ml (17.4 ng/ml), and these concentrations maintained at approximately 9.6 ng/
ml (4.6 ng/ml) for 7 days following dosing. This formulation is compounded and has not completed FDA investigation, which may increase formulation variability as it is produced or stored. The lack of control groups and potential bias in lesion grading are additional recognised limitations. The results of this study provide preliminary safety and efficacy data with regard to a novel LAO-USA formulation. Future study is warranted to describe safety and efficacy for both ESGD and EGGD and would support further FDA investigation.
Introduction
Equine gastric ulcer syndrome (EGUS) is an inclusive term describing the erosive and potentially ulcerative pathology of
the stomach. EGUS is further classified as equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD) that more specifically defines the affected region of the stomach (Sykes, 2019; Sykes et al., 2015b). ESGD has been assumed to be related to exposure of mucosa not accustomed to acidity, whereas EGGD results from breakdown of the normal defence mechanisms that protect the mucosa from acidic gastric contents (Luthersson et al., 2009; Rendle et al., 2018a; Sykes, 2019; Sykes et al., 2015b). ESGD is highly prevalent in horses of multiple disciplines (Andrews et al., 1999; Begg & O’Sullivan, 2003; Dionne et al., 2003; Feige et al., 2002; Goncalves et al., 2002; Johnson et al., 2001; Le Jeune et al., 2009; Luthersson et al., 2009; McClure et al., 1999; Murray, 1991, 1996; Mitchell, 2001; Nieto et al., 2004; Tamzali et al., 2011) with Thoroughbred racehorses in training have reported prevalence of up to 100% (Murray et al., 1996). The prevalence of EGGD has been shown to range from 27 to 64%, dependent on breed and level of training (Andrews et al., 1999; Husted et al., 2010; Nieto et al., 2004; Sykes et al., 2015a; Tamzali et al., 2011). Oral omeprazole [Gastrogard: Merial LLC] (GG) has
historically been the treatment of choice for EGUS with more recent studies looking into other effective therapies of both ESGD and EGGD (Di Salvo et al., 2016; Jenkins et al., 1992; Rendle et al., 2018a,b; Sykes, 2019; Sykes et al., 2015b, 2017a; Varley et al., 2019). Current label dosing is daily GG (4 mg/kg bwt) for 28 days, although updated recommendations provide more specific dosing regimens for either ESGD or EGGD, in both cases to be followed by gastroscopic reassessment to evaluate degree of healing (Sykes et al., 2015b). It has recently been demonstrated that ad libitum hay diets, which are commonly recommended in the management of EGUS (Goncalves et al., 2002; Nadeau et al., 2000; Sykes, 2019; Sykes et al., 2015b), reduce the bioavailability (Sykes, 2019) and impair the ability to raise intragastric pH (Sykes et al., 2017b) of GG. In addition, a high variation in bioavailability of omeprazole has been documented between horses (Sykes et al., 2014). These considerations may contribute to the variability in efficacy of treatment observed with horses following oral dosing. Parental administration would be expected to bypass complications with feeding and individual variation impacts on bioavailability. Additional potential benefits of LAO formulations include improved owner and patient compliance if a decreased dosing frequency could be established than is currently available with daily GG.
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