Pharmacokinetic and pharmacodynamic effects of 2 registered omeprazole preparations and varying dose rates in horses.
Abstract: Omeprazole preparations vary in bioavailability in horses. Objective: To characterize the pharmacokinetics and pharmacodynamics of an existing enteric-coated oral omeprazole paste (REF) and a novel, in-feed, enteric-coated dry granule preparation (NOV). Methods: Twelve Standardbred/Thoroughbred mares free from clinical disease. Methods: A prospective, blinded randomized interventional study was trial, conducted in 3 parts: (a) bioavailability study, (b) dose titration study, and (c) comparative clinical pharmacodynamic study, each using a blocked crossover design. Results: Consistent with the larger dose administered, Cmax (median, 1032 ng/mL; range, 576-1766) and AUC0-24 (median, 63.9 μg/mL*min; range, 42.4-152.4) were greater after single oral administration of NOV than REF (282.7 ng/mL; range, 94.8-390.2, and 319 23.8 μg/mL*min; range, 8.2-42.3, respectively; both P = .004). No differences were observed between products for absolute oral bioavailability (NOV 55% range, 15-88; REF 17% range, 10-77; P = .25). Treatment with both preparations was associated with reduced gastric squamous ulcer scores and increased pH of gastric fluid. Bioequivalence was demonstrated for pharmacodynamic measures with the exception of % time pH <4, despite differences in dose rate and subsequent plasma omeprazole concentrations. Conclusions: The findings of this study indicate that the NOV product would be a suitable alternative to the reference product, and confirm that plasma concentrations of omeprazole and omeprazole dose do not predict drug pharmacodynamics in horses.
© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Publication Date: 2020-12-19 PubMed ID: 33340169PubMed Central: PMC7848319DOI: 10.1111/jvim.15971Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Veterinary
Summary
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This research investigates the bioavailability of two types of omeprazole preparations in horses. The study found both preparations to be associated with reduced gastric ulcer scores and increased gastric fluid pH. This research suggests that omeprazole plasma concentrations and dose don’t directly correlate to drug actions in horses.
Study Design and Approach
- The study was a prospective, blinded, randomized interventional trial conducted in three parts. Participating subjects were twelve disease-free Standardbred/Thoroughbred mares.
- The three part study included a bioavailability study, a dose titration study, and a comparative clinical pharmacodynamic study. Each was conducted using a blocked crossover design which redistributes the subjects across different intervention groups to negate possible period effects.
Investigated Omeprazole Preparations
- The researchers used two types of omeprazole preparations. One was a pre-existing enteric-coated oral omeprazole paste (REF), and the other was a novel, in-feed, enteric-coated dry granule preparation (NOV).
- Omeprazole is a medication used in horses primarily for the treatment of gastric ulcers. The enteric-coated form of the drug is designed to resist destruction by stomach acid, enhancing its bioavailability.
Results of the Study
- The values achieved for the concentration of omeprazole in the blood over time (Cmax) and the area under the curve (AUC0-24), used to measure drug exposure, were higher for NOV due to the larger dosage administered.
- No significant differences between both products were observed in terms of absolute oral bioavailability, which is the proportion of the drug that enters circulation and is able to have an active effect.
- The treatment with both preparations was associated with reduced gastric squamous ulcer scores and increased pH of gastric fluid, indicating a reduction in stomach acidity.
- For most pharmacodynamic measures, the two preparations were found to be bioequivalent. The only exception was the percentage of time with pH<4, which despite different dose rates and plasma omeprazole concentrations, did not vary significantly between the two treatments.
Conclusions from the Study
- Based on the findings of the study, it is concluded that the novel omeprazole product (NOV) is a suitable alternative to the reference product (REF).
- The study confirms that in horses, the plasma concentrations of omeprazole and the dosage of the drug do not necessarily predict the pharmacodynamic effects of the drug, i.e., its therapeutic effects.
Cite This Article
APA
Wise JC, Hughes KJ, Edwards S, Jacobson GA, Narkowicz CK, Raidal SL.
(2020).
Pharmacokinetic and pharmacodynamic effects of 2 registered omeprazole preparations and varying dose rates in horses.
J Vet Intern Med, 35(1), 620-631.
https://doi.org/10.1111/jvim.15971 Publication
Researcher Affiliations
- School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
- School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
- School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
- School of Pharmacy and Pharmacology, University of Tasmania, Hobart, Tasmania, Australia.
- School of Pharmacy and Pharmacology, University of Tasmania, Hobart, Tasmania, Australia.
- School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
MeSH Terms
- Administration, Oral
- Animals
- Anti-Ulcer Agents / pharmacology
- Anti-Ulcer Agents / therapeutic use
- Cross-Over Studies
- Female
- Horse Diseases / drug therapy
- Horses
- Omeprazole / pharmacology
- Omeprazole / therapeutic use
- Prospective Studies
- Stomach Ulcer / drug therapy
- Stomach Ulcer / veterinary
Grant Funding
- Equestra Pty Ltd
Conflict of Interest Statement
The funder Equestra Pty Ltd did not influence the design or conduct of the study, assessment of the data, or writing of the manuscript. The authors have no conflicts of interest.
References
This article includes 35 references
- Sykes BW, Hewetson M, Hepburn RJ, Luthersson N, Tamzali Y. European College of Equine Internal Medicine Consensus Statement; equine gastric ulcer syndrome in adult horses.. J Vet Intern Med 2015;29:1288‐1299.
- Begg LM, O'Sullivan CB. The prevalence and distribution of gastric ulceration in 345 racehorses.. Aust Vet J 2003;81:199‐201.
- Jonsson H, Egenvall A. Prevalence of gastric ulceration in Swedish Standardbreds in race training.. Equine Vet J 2006;38:209‐213.
- Rabuffo TS, Orsini JA, Sullivan E, Engiles J, Norman T, Boston R. Associations between age or sex and prevalence of gastric ulceration in Standardbred racehorses in training.. J Am Vet Med Assoc 2002;221:1156‐1159.
- Bell RJW, Kingston JK, Mogg TD, Perkins NR. The prevalence of gastric ulceration in racehorses in New Zealand.. New Zeal Vet J 2007;55:13‐18.
- Andrews FM, Nadeau JA. Clinical syndromes of gastric ulceration in foals and mature horses.. Equine Vet J 1999;31:30‐33.
- Murray MJ, Schusser GR, Pipers FS. Factors associated with gastric lesions in thoroughbred racehorses.. Equine Vet J 1996;28:368‐374.
- Sykes BW, Sykes KM, Hallowell GD. A comparison of two doses of omeprazole in the treatment of equine gastric ulcer syndrome: a blinded, randomised, clinical trial.. Equine Vet J 2014;46:416‐421.
- Andrews FM, Nadeau JA. Clinical syndromes of gastric ulceration in foals and mature horses.. Equine Vet J 1999;29:30.
- MacAllister CG, Sifferman RL, McClure SR. Effects of omeprazole paste on healing of spontaneous gastric ulcers in horses and foals: a field trial.. Equine Vet J 1999;31:77‐80.
- Sykes BW, Sykes K, Hallowell GD. Comparison of the effect of two doses of omeprazole on the squamous gastric mucosa in thoroughbred racehorses.. Vet Rec 2014;175:249.
- Sykes BW, Sykes KM, Hallowell GD. A comparison between pre‐ and post exercise administration of omeprazole in the treatment of equine gastric ulcer syndrome: a blinded, randomised, clinical trial.. Equine Vet J 2014;46:422‐426.
- Daurio CP, Holste JE, Andrews FM. Effect of omeprazole paste on gastric acid secretion in horses.. Equine Vet J 1999;31:59‐62.
- Andrews FM, Sifferman RL, Bernard W. Efficacy of omeprazole paste in the treatment and prevention of gastric ulcers in horses.. Equine Vet J 1999;31:81‐86.
- Sykes BW, Underwood C, McGowan CM. The effects of dose and diet on the pharmacokinetics of omeprazole in the horse.. J Vet Pharmacol Ther 2017;40:172‐178.
- Sykes BW, Underwood C, McGowan CM. Pharmacokinetics of intravenous, plain oral and enteric‐coated oral omeprazole in the horse.. J Vet Pharm Ther 2015;38:130‐136.
- Sykes BW, Underwood C, McGowan CM. The effect of feeding on the pharmacokinetic variables of two commercially available formulations of omeprazole.. J Vet Pharmacol Ther 2015;38:500‐503.
- Andersson T, Andren K, Cederberg C, Lagerstrom PO, Lundborg P, Skanberg I. Pharmacokinetics and bioavailability of omeprazole after single and repeated oral administration in healthy subjects.. British J Clin Pharm 1990;29:557‐563.
- Sykes BW, Underwood C, Greer R, McGowan CM, Mills PC. The effects of dose and diet on the pharmacodynamics of omeprazole in the horse.. Equine Vet J 2017;49:525‐531.
- Raidal SL, Andrews FM, Nielsen SG, Trope G. Pharmacokinetic and pharmacodynamic effects of two omeprazole formulations on stomach pH and gastric ulcer scores.. Equine Vet J 2017;49:802‐809.
- Birkmann K, Junge HK, Maischberger E, Wehrli Eser M, Schwarzwald CC. Efficacy of omeprazole powder paste or enteric‐coated formulation in healing of gastric ulcers in horses.. J Vet Intern Med 2014;28:925‐933.
- Zhang Y, Huo M, Zhou J, Xie S. PKSolver: an add‐in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel.. Comp Meth Prog Biomed 2010;99:306‐314.
- Whitmire ML, Ammerman J, Pd L. LC‐MS/MS bioanalysis method development, validation, and sample analysis: points to consider when conducting nonclinical and clinical studies in accordance with current regulatory guidances.. J Anal Bioanal Tech 2011;(S4):1‐10.
- Sykes BW, Sykes KM, Hallowell GD. A comparison of three doses of omeprazole in the treatment of equine gastric ulcer syndrome: a blinded, randomised, dose‐response clinical trial.. Equine Vet J 2015;47:285‐290.
- Cederberg C, Andersson T, Skanberg I. Omeprazole: pharmacokinetics and metabolism in man.. Scand J Gastro Supp 1989;166:33‐40. discussion 41‐32.
- Regardh CG, Gabrielsson M, Hoffman KJ. Pharmacokinetics and metabolism of omeprazole in animals and man—an overview.. Scand J Gastro Supp 1985;108:79‐94.
- Oosterhuis B, Jonkman JH. Omeprazole: pharmacology, pharmacokinetics and interactions.. Digestion 1989;44(Suppl 1):9‐17.
- Jenkins CC, Frazier DL, Blackford JT. Pharmacokinetics and antisecretory effects of intravenous omeprazole in horses.. Equine Vet J 1992;24:84‐88.
- Viljanto M, Hillyer L, Hincks P, Pearce C, Paine SW. Re‐evaluation of the regulation of omeprazole in racehorses: an evidence‐based approach.. J Vet Pharmacol Ther 2018;41:469‐475.
- Merritt AM, Sanchez LC, Burrow JA, Church M, Ludzia S. Effect of GastroGard and three compounded oral omeprazole preparations on 24 h intragastric pH in gastrically cannulated mature horses.. Equine Vet J 2003;35:691‐695.
- Sykes BW, McGowan CM, Mills PC. Placement of an indwelling percutaneous gastrotomy (PEG) tube for the measurement of intra‐gastric pH in two horses.. Equine Vet Educat 2015;27:627‐632.
- Husted L, Sanchez LC, Baptiste KE. Effect of a feed/fast protocol on pH in the proximal equine stomach.. Equine Vet J 2009;41:658‐662.
- Husted L, Sanchez LC, Olsen SN. Effect of paddock vs. stall housing on 24 hour gastric pH within the proximal and ventral equine stomach.. Equine Vet J 2008;40:337‐341.
- Solana MJ, Lopez‐Herce J, Sanchez C. Comparison of continuous pH‐meter and intermittent pH paper monitoring of gastric pH in critically ill children.. Europ J Ggastroent Hepat 2012;24:33‐36.
- Sykes B, Jokisalo JM. Rethinking equine gastric ulcer syndrome: part 3 ‐ equine glandular gastric ulcer syndrome (EGGUS).. Equine Vet Educat 2015;27:372‐375.
Citations
This article has been cited 3 times.- Hodgson E, Thirouin M, Narayanan P, Romano TR, Wise J, Bond S. A novel placement method of a calibration-free pH capsule for continuous wireless measurement of intragastric pH in horses. J Vet Intern Med 2025 Jan-Feb;39(1):e17273.
- Williams Louie E, Nieto J, Wensley F, Morgan JM, Finno CJ, Berryhill EH. Efficacy of the oral supplement, Equine Omega Complete, for the prevention of gastric ulcers and alpha-tocopherol supplementation in horses. J Vet Intern Med 2023 Nov-Dec;37(6):2529-2534.
- Hewetson M, Tallon R. Equine Squamous Gastric Disease: Prevalence, Impact and Management. Vet Med (Auckl) 2021;12:381-399.
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