Pharmacokinetics of methylprednisolone acetate after intra-articular administration and subsequent suppression of endogenous hydrocortisone secretion in exercising horses

Maria I. Menéndez Comparative Orthopaedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Mitch A. Phelps Department of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210.

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Elijah A. Hothem Department of Orthopedics, College of Medicine, The Ohio State University, Columbus, OH 43210.

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Alicia L. Bertone Comparative Orthopaedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Abstract

Objective—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.

Animals—Five 3-year-old Thoroughbred mares.

Procedures—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 and Clinical Relevance—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.

Abstract

Objective—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.

Animals—Five 3-year-old Thoroughbred mares.

Procedures—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 and Clinical Relevance—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.

Contributor Notes

Supported by Pfizer Inc and the United States Equestrian Federation.

The authors thank Drs. Akikazu Ishihara, Stephen Schumacher, Thomas Lomangino, Jennifer Dulin, Emily Falk, Carissa Norquest, and Brian Johnson for technical assistance; Dr. Steven Kamerling for assistance with data analysis; and Tim Vojt for assistance with preparation of illustrations.

Address correspondence to Dr. Bertone (bertone.1@osu.edu).
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