Use of plasma creatine kinase pharmacokinetics to estimate the amount of exercise-induced muscle damage in Beagles

Guillaume P. Chanoit Unité Mixte de Recherche 181 Physiopathologie et Toxicologie Expérimentales, Institut National de la Recherche Agronomique, National Veterinary School, 31076 Toulouse cedex 03, France.
Present address Department of Small Animal Medicine and Surgery, National Veterinary School of Lyon, 69280 Marcy l'Etoile, France.

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Hervé P. Lefebvre Unité Mixte de Recherche 181 Physiopathologie et Toxicologie Expérimentales, Institut National de la Recherche Agronomique, National Veterinary School, 31076 Toulouse cedex 03, France.

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Karine Orcel Unité Mixte de Recherche 181 Physiopathologie et Toxicologie Expérimentales, Institut National de la Recherche Agronomique, National Veterinary School, 31076 Toulouse cedex 03, France.

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Valérie Laroute Unité Mixte de Recherche 181 Physiopathologie et Toxicologie Expérimentales, Institut National de la Recherche Agronomique, National Veterinary School, 31076 Toulouse cedex 03, France.

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Pierre-Louis Toutain Unité Mixte de Recherche 181 Physiopathologie et Toxicologie Expérimentales, Institut National de la Recherche Agronomique, National Veterinary School, 31076 Toulouse cedex 03, France.

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Jean-Pierre Braun Unité Mixte de Recherche 181 Physiopathologie et Toxicologie Expérimentales, Institut National de la Recherche Agronomique, National Veterinary School, 31076 Toulouse cedex 03, France.

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Abstract

Objective—To assess the effects of moderate exercise on plasma creatine kinase (CK) pharmacokinetics and to estimate exercise-induced muscle damage in dogs.

Animals—6 untrained adult Beagles.

Procedure—The study was divided into 3 phases. In phase 1, dogs ran for 1 hour at a speed of 9 km/h, and samples were used to determine the area under the plasma CK activity versus time curve (AUC) induced by exercise. In phases 2 and 3, pharmacokinetics of CK were calculated in dogs during exercise and at rest, respectively. Values for AUC and plasma clearance (Cl) were used to estimate muscle damage.

Results—At rest, values for Cl, steady-state volume of distribution (Vdss), and mean retention time (MRT) were 0.32 ± 0.02 ml/kg of body weight/min, 57 ± 17.3 ml/kg, and 3.0 ± 0.57 h, respectively. During exercise, Cl decreased significantly (0.26 ± 0.03 ml/kg/min), MRT increased significantly, (4.4 ± 0.97 h), and Vdss remained unchanged. Peak of plasma CK activity (151 ± 58.8 U/L) was observed 3 hours after completion of exercise. Estimated equivalent amount of muscle corresponding to the quantity of CK released was 41 ± 29.3 mg/kg.

Conclusion and Clinical Relevance—These results revealed that exercise had a minor effect on CK disposition and that the equivalent amount of muscle damaged by moderate exercise was negligible. This study illustrates the relevance for use of the minimally invasive and quantitative pharmacokinetic approach when estimating muscle damage. (Am J Vet Res 2001;62:1375–1380)

Abstract

Objective—To assess the effects of moderate exercise on plasma creatine kinase (CK) pharmacokinetics and to estimate exercise-induced muscle damage in dogs.

Animals—6 untrained adult Beagles.

Procedure—The study was divided into 3 phases. In phase 1, dogs ran for 1 hour at a speed of 9 km/h, and samples were used to determine the area under the plasma CK activity versus time curve (AUC) induced by exercise. In phases 2 and 3, pharmacokinetics of CK were calculated in dogs during exercise and at rest, respectively. Values for AUC and plasma clearance (Cl) were used to estimate muscle damage.

Results—At rest, values for Cl, steady-state volume of distribution (Vdss), and mean retention time (MRT) were 0.32 ± 0.02 ml/kg of body weight/min, 57 ± 17.3 ml/kg, and 3.0 ± 0.57 h, respectively. During exercise, Cl decreased significantly (0.26 ± 0.03 ml/kg/min), MRT increased significantly, (4.4 ± 0.97 h), and Vdss remained unchanged. Peak of plasma CK activity (151 ± 58.8 U/L) was observed 3 hours after completion of exercise. Estimated equivalent amount of muscle corresponding to the quantity of CK released was 41 ± 29.3 mg/kg.

Conclusion and Clinical Relevance—These results revealed that exercise had a minor effect on CK disposition and that the equivalent amount of muscle damaged by moderate exercise was negligible. This study illustrates the relevance for use of the minimally invasive and quantitative pharmacokinetic approach when estimating muscle damage. (Am J Vet Res 2001;62:1375–1380)

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