Pharmacokinetics and pharmacodynamics of dexamethasone after oral administration in apparently healthy horses.
Abstract: To assess pharmacokinetic and pharmacodynamic properties of dexamethasone administered PO as a solution or powder, compared with properties of dexamethasone solution administered IV, in apparently healthy horses. Methods: 6 adult horses. Methods: Serum cortisol concentration for each horse was determined before each treatment (baseline values). Dexamethasone (0.05 mg/kg) was administered PO (in solution or powdered form) or IV (solution) to horses from which feed had or had not been withheld (unfed and fed horses, respectively). Each horse received all 6 treatments in random order at 2-week intervals; PO and IV administrations of dexamethasone were accompanied by IV or PO sham treatments, respectively. Plasma dexamethasone and serum cortisol concentrations were assessed at predetermined intervals. Results: Maximum plasma dexamethasone concentration after PO administration of powdered dexamethasone in unfed horses was significantly higher than the maximum plasma concentration after PO administration of dexamethasone solution in unfed or fed horses. Mean bioavailability of dexamethasone ranged from 28% to 66% but was not significantly different among horses receiving either formulation PO in the unfed or fed state. After dexamethasone treatment PO or IV, serum cortisol concentrations were significantly less than baseline at 1 to 72 hours in unfed horses and at 2 to 48 hours in fed horses. Conclusions: PO or IV administration of dexamethasone resulted in suppression of cortisol secretion in unfed and fed adult horses; the magnitude of suppression did not differ among treatment groups, and serum cortisol concentrations returned to baseline after 48 to 72 hours.
Publication Date: 2010-07-03 PubMed ID: 20594087DOI: 10.2460/ajvr.71.7.831Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study explores how dexamethasone, given orally as a solution or powder or intravenously, behaves in healthy horses’ bodies and how it influences cortisol levels, comparing the outcomes between fed and unfed horses.
Objective and Method
- The researchers aimed to understand the pharmacokinetics (how the drug moves within the body) and pharmacodynamics (the drug’s effects on the body) of dexamethasone, a type of medication, when administered orally (in solution or powdered form) or intravenously (IV) in horses. This evaluation was conducted on both fed and unfed horses.
- Six adult horses were involved in the study. Dexamethasone was given to each horse in all three ways, with sham treatments accompanying each method. The administration of treatments was done in a randomized order, with a 2-week gap between each treatment session.
- Serum cortisol levels were measured before each treatment to establish baseline values. Subsequent plasma dexamethasone and serum cortisol levels were assessed at set intervals after the treatment.
Results
- In unfed horses, the highest recorded plasma dexamethasone concentration was achieved after oral administration of the powdered form of the drug. This was significantly higher than that achieved after either oral administration of the drug solution or after feeding the horses.
- The bioavailability of the drug, which means the amount that is absorbed and ready to use in the body, ranged from 28% to 66%, with no significant difference observed between horses given the drug orally, whether in the fed or unfed state.
- Following dexamethasone treatment, serum cortisol levels decreased significantly below baseline values for 1 to 72 hours in unfed horses and for 2 to 48 hours in fed horses.
Conclusion
- Regardless of the administration method or feeding state of the horse, dexamethasone suppressed cortisol secretion significantly in all adult horses. The suppression’s intensity did not vary across the treatment groups, and cortisol levels returned to baseline within 48 to 72 hours post-treatment.
- This insight is valuable for optimizing dexamethasone use in horses, potentially improving its therapeutic efficacy and minimizing any potential side effects.
Cite This Article
APA
Grady JA, Davis EG, Kukanich B, Sherck AB.
(2010).
Pharmacokinetics and pharmacodynamics of dexamethasone after oral administration in apparently healthy horses.
Am J Vet Res, 71(7), 831-839.
https://doi.org/10.2460/ajvr.71.7.831 Publication
Researcher Affiliations
- Veterinary Medical Teaching Hospital, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA. dr.grady@sapulpaequine.com
MeSH Terms
- Administration, Oral
- Animals
- Anti-Inflammatory Agents / blood
- Anti-Inflammatory Agents / pharmacokinetics
- Anti-Inflammatory Agents / pharmacology
- Area Under Curve
- Circadian Rhythm / drug effects
- Dexamethasone / blood
- Dexamethasone / pharmacokinetics
- Dexamethasone / pharmacology
- Female
- Half-Life
- Horses / physiology
- Hospitalization
- Hospitals, Animal
- Hydrocortisone / blood
- Kinetics
- Male
- Orchiectomy
Citations
This article has been cited 8 times.- Cox A, Stewart AJ. Insect Bite Hypersensitivity in Horses: Causes, Diagnosis, Scoring and New Therapies.. Animals (Basel) 2023 Aug 4;13(15).
- Kikuchi M, Nagata SI, Ishige T, Minamijima Y, Hirota KI, Tozaki T, Kakoi H, Kizaki K. Evaluation of the effect of glucocorticoid treatment on adrenocortical functions by monitoring endogenous hydrocortisone in horses.. J Vet Med Sci 2023 Jun 13;85(6):647-652.
- Mainguy-Seers S, Lavoie JP. Glucocorticoid treatment in horses with asthma: A narrative review.. J Vet Intern Med 2021 Jul;35(4):2045-2057.
- Pitel MO, Heller MC, Roberson JR, McKenzie EC, Sinnott DM, Affolter VK. Lymphoplasmacytic and eosinophilic enteritis with or without globule leukocyte hyperplasia in 4 goats.. J Vet Intern Med 2021 May;35(3):1620-1625.
- de Wasseige S, Picotte K, Lavoie JP. Nebulized dexamethasone sodium phosphate in the treatment of horses with severe asthma.. J Vet Intern Med 2021 May;35(3):1604-1611.
- Ekstrand C, Bondesson U, Giving E, Hedeland M, Ingvast-Larsson C, Jacobsen S, Löfgren M, Moen L, Rhodin M, Saetra T, Ranheim B. Disposition and effect of intra-articularly administered dexamethasone on lipopolysaccharide induced equine synovitis.. Acta Vet Scand 2019 Jun 20;61(1):28.
- Held F, Ekstrand C, Cvijovic M, Gabrielsson J, Jirstrand M. Modelling of oscillatory cortisol response in horses using a Bayesian population approach for evaluation of dexamethasone suppression test protocols.. J Pharmacokinet Pharmacodyn 2019 Feb;46(1):75-87.
- Hirsch G, Lavoie-Lamoureux A, Beauchamp G, Lavoie JP. Neutrophils are not less sensitive than other blood leukocytes to the genomic effects of glucocorticoids.. PLoS One 2012;7(9):e44606.
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