Influence of exercise on the distribution of technetium Tc 99m medronate following intra-articular injection in horses

Jennifer A. Dulin Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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W. Tod Drost Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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

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Elizabeth M. Santschi Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Maria I. Menendez Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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

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Abstract

Objective—To determine the effects of exercise on the distribution and pharmacokinetics of technetium Tc 99m medronate (99mTc-MDP) following intra-articular (IA) injection in horses.

Animals—5 horses.

Procedures—1 antebrachiocarpal joint (ACJ)/horse was assigned to the exercised group (n = 5), and the contralateral ACJ was evaluated in the nonexercised group (5) after a minimum washout period of 7 days. Following IA injection of 99mTc-MDP (148 MBq), blood and scintigraphic images of the carpus were obtained at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 240, 360, 480, 600, 720, and 1,440 minutes. Plasma and scintigraphic radioactivity were determined over time, and pharmacokinetic parameters were generated via noncompartmental and compartmental analyses. Each horse was monitored via physical and lameness examination and ACJ synovial fluid analysis before injection and at days 1, 2, 3, and 7

Results—Lameness was not observed. Mean ± SD synovial fluid WBC count increased at day 1 (exercised, 721 ± 234 cells/μL; nonexercised, 948 ± 223 cells/μL), but returned to baseline at days 3 and 7 Mean time to maximum plasma radioactivity was earlier in the exercised group (16.00 ± 2.35 minutes) than the nonexercised group (43.75 ± 3.64 minutes). Linear regression of the scintigraphic radioactivity-time curves revealed a greater negative slope in the exercised group within the first 25 minutes. There was no difference in absorption or elimination rate constants in a 2-compartment model.

Conclusions and Clinical Relevance—IA injection of 99mTc-MDP was safe and effective for evaluating synovial solute distribution. Exercise significantly increased early transfer of 99mTc-MDP from the ACJ into plasma, although absorption and elimination rate constants were not affected. Exercise may affect synovial clearance and withdrawal times of medications administered IA.

Abstract

Objective—To determine the effects of exercise on the distribution and pharmacokinetics of technetium Tc 99m medronate (99mTc-MDP) following intra-articular (IA) injection in horses.

Animals—5 horses.

Procedures—1 antebrachiocarpal joint (ACJ)/horse was assigned to the exercised group (n = 5), and the contralateral ACJ was evaluated in the nonexercised group (5) after a minimum washout period of 7 days. Following IA injection of 99mTc-MDP (148 MBq), blood and scintigraphic images of the carpus were obtained at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 240, 360, 480, 600, 720, and 1,440 minutes. Plasma and scintigraphic radioactivity were determined over time, and pharmacokinetic parameters were generated via noncompartmental and compartmental analyses. Each horse was monitored via physical and lameness examination and ACJ synovial fluid analysis before injection and at days 1, 2, 3, and 7

Results—Lameness was not observed. Mean ± SD synovial fluid WBC count increased at day 1 (exercised, 721 ± 234 cells/μL; nonexercised, 948 ± 223 cells/μL), but returned to baseline at days 3 and 7 Mean time to maximum plasma radioactivity was earlier in the exercised group (16.00 ± 2.35 minutes) than the nonexercised group (43.75 ± 3.64 minutes). Linear regression of the scintigraphic radioactivity-time curves revealed a greater negative slope in the exercised group within the first 25 minutes. There was no difference in absorption or elimination rate constants in a 2-compartment model.

Conclusions and Clinical Relevance—IA injection of 99mTc-MDP was safe and effective for evaluating synovial solute distribution. Exercise significantly increased early transfer of 99mTc-MDP from the ACJ into plasma, although absorption and elimination rate constants were not affected. Exercise may affect synovial clearance and withdrawal times of medications administered IA.

Contributor Notes

Dr. Dulin's present address is the Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

Funded in part by the United States Equestrian Federation.

The authors thank Dr. Akikazu Ishihara, Brian Johnson, Emily Falk, and Tim Vojt for assistance.

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