Pharmacokinetics of methylprednisolone acetate after intra-articular administration and subsequent suppression of endogenous hydrocortisone secretion in exercising horses.
Abstract: To determine the pharmacokinetics of methylprednisolone (MP) and the relationship between MP and hydrocortisone (HYD) concentrations in plasma and urine after intra-articular (IA) administration of 100 or 200 mg of MP acetate (MPA) to horses. Methods: Five 3-year-old Thoroughbred mares. Methods: Horses exercised on a treadmill 3 times/wk during the study. Horses received 100 mg of MPA IA, then 8 weeks later received 200 mg of MPA IA. Plasma and urine samples were obtained at various times for 8 weeks after horses received each dose of MPA; concentrations of MP and HYD were determined. Pharmacokinetic-pharmacodynamic estimates for noncompartmental and compartmental parameters were determined. Results: Maximum concentration of MP in plasma was similar for each MPA dose; concentrations remained greater than the lower limit of quantitation for 18 and 7 days after IA administration of 200 and 100 mg of MPA, respectively. Maximum concentration and area under the observed concentration-time curve for MP in urine were significantly higher (approximately 10-and 17-fold, respectively) after administration of 200 versus 100 mg of MPA. Hydrocortisone concentration was below quantifiable limits for ≥ 48 hours in plasma and urine of all horses after administration of each MPA dose. Conclusions: Pharmacokinetics of MP may differ among IA MPA dosing protocols, and MP may be detected in plasma and urine for a longer time than previously reported. This information may aid veterinarians treating sport horses. Further research is warranted to determine whether plasma HYD concentration can aid identification of horses that received exogenous glucocorticoids.
Publication Date: 2012-08-29 PubMed ID: 22924728DOI: 10.2460/ajvr.73.9.1453Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research is aimed at studying the pharmacokinetics of methylprednisolone (MP), its relationship with hydrocortisone (HYD), and their presence in the plasma and urine of horses after intra-articular administration. The study also attempts to understand how these findings might aid in identifying use of glucocorticoids in horses and help in their treatment.
Methodology
- The study was conducted on five Thoroughbred mares of three years old.
- The horses were made to exercise on a treadmill thrice a week during the study period.
- Initially, the horses were given 100 mg of methylprednisolone acetate (MPA) intra-articularly. Eight weeks later, they received a larger dose of 200 mg of MPA in the same manner.
- Following administration of each dose of MPA, plasma and urine samples were collected at various points for eight weeks. These samples were examined to determine the concentrations of MP and HYD.
- Compartmental and non-compartmental pharmacokinetic-pharmacodynamic parameters were then established based on these concentrations.
Results
- The maximum concentration of MP in plasma was found to be similar for both MPA doses. These concentrations stayed significantly higher than the lower limit of quantitation for 18 days post administration of 200 mg of MPA, and for 7 days following 100 mg of MPA administration.
- Both the maximum concentration and the area under the observed concentration-time curve for MP in urine were about 10 times and 17 times higher respectively, after the 200 mg MPA dose compared to the 100 mg dose.
- After administration of both MPA doses, the HYD concentration in the plasma and urine of all the horses dropped below quantifiable limits for at least 48 hours.
Conclusion
- The research concludes that the pharmacokinetics of MP may vary based on different intra-articular MPA dosing regimes, and that MP may be detected in plasma and urine for a longer duration than previously documented.
- This information may assist veterinarians in better treating sport horses. The study also suggests further research to determine whether assessing plasma HYD concentration can help in identifying those horses which have received exogenous glucocorticoids.
Cite This Article
APA
Menéndez MI, Phelps MA, Hothem EA, Bertone AL.
(2012).
Pharmacokinetics of methylprednisolone acetate after intra-articular administration and subsequent suppression of endogenous hydrocortisone secretion in exercising horses.
Am J Vet Res, 73(9), 1453-1461.
https://doi.org/10.2460/ajvr.73.9.1453 Publication
Researcher Affiliations
- Comparative Orthopaedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents / administration & dosage
- Anti-Inflammatory Agents / blood
- Anti-Inflammatory Agents / pharmacokinetics
- Anti-Inflammatory Agents / urine
- Area Under Curve
- Female
- Horses / blood
- Horses / physiology
- Horses / urine
- Hydrocortisone / blood
- Hydrocortisone / metabolism
- Hydrocortisone / urine
- Methylprednisolone / administration & dosage
- Methylprednisolone / analogs & derivatives
- Methylprednisolone / blood
- Methylprednisolone / pharmacokinetics
- Methylprednisolone / urine
- Methylprednisolone Acetate
- Physical Conditioning, Animal / physiology
- Random Allocation
- Secretory Rate / drug effects
Citations
This article has been cited 1 times.- 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.
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