Pharmacokinetic variables and bioavailabiljty from muscle of creatine kinase in cattle

Dr Hervé P. Lefebvre From the Département de Physiopathologie et URA INRA de Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire, 23 chemin des Capelles, 31076 Toulouse Cedex, France.

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Dr Pierre-Louis Toutain From the Département de Physiopathologie et URA INRA de Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire, 23 chemin des Capelles, 31076 Toulouse Cedex, France.

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Jean-Paul Serthelon From the Département de Physiopathologie et URA INRA de Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire, 23 chemin des Capelles, 31076 Toulouse Cedex, France.

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Dr Véronique Lassourd From the Département de Physiopathologie et URA INRA de Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire, 23 chemin des Capelles, 31076 Toulouse Cedex, France.

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Dr Laure Gardey From the Département de Physiopathologie et URA INRA de Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire, 23 chemin des Capelles, 31076 Toulouse Cedex, France.

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Dr Jean-Pierre Braun From the Département de Physiopathologie et URA INRA de Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire, 23 chemin des Capelles, 31076 Toulouse Cedex, France.

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Summary

Pharmacokinetic variables of skeletal muscle creatine kinase (ck) activity after iv administration of a muscle extract; ck bioavailability after im administration of the muscle extract; and effect of im administration of saline solution, to appreciate the possible release of ck consecutive to muscle puncture, were determined in 6 cows. A general equation for the quantitative estimation of skeletal muscle damage also was derived.

Administration of saline solution im had no effect on plasma ck activity (anova, P > 0.05) in any of the cows. After iv administration of the muscle extract (150 U/kg of body weight), mean volume of the central compartment, plasma half-life, and plasma clearance of ck were 0.027 ± 0.007 L/kg, 520 ± 109 minutes, and 6.43 ± 2.29 ml/kg/h, respectively. After im administration (150 U/kg), mean bioavailability of ck was 51 ± 17% and maximal plasma ck activity (500 ± 97 U/L) was observed at 454 ± 131 minutes. The rate of ck activity entry into plasma was determined by use of deconvolution analysis. Two peaks were observed; the first appeared before the 30th minute after im administration, and the second appeared at 3.3 ± 1.1 hours. Amplitudes were 6.31 ± 4.45 and 6.57 ± 3.08 U/kg/h, for the first and the second peaks, respectively. The quantity of ck liberated from control muscle was 0.69 ± 0.12 U/kg/h, corresponding to a normal daily catabolism of 5.8 ± 1.0 mg of muscle/kg. From these results, the following equation can be proposed to determine the corresponding mean equivalent of destroyed muscle (Qmuscle, test article) after im administration of a test article:

Qmuscle, test article (g/kg) = 4.41 · 10-6. auc (U/h/L), with auc being the ck plasma activity area under the curve.

Summary

Pharmacokinetic variables of skeletal muscle creatine kinase (ck) activity after iv administration of a muscle extract; ck bioavailability after im administration of the muscle extract; and effect of im administration of saline solution, to appreciate the possible release of ck consecutive to muscle puncture, were determined in 6 cows. A general equation for the quantitative estimation of skeletal muscle damage also was derived.

Administration of saline solution im had no effect on plasma ck activity (anova, P > 0.05) in any of the cows. After iv administration of the muscle extract (150 U/kg of body weight), mean volume of the central compartment, plasma half-life, and plasma clearance of ck were 0.027 ± 0.007 L/kg, 520 ± 109 minutes, and 6.43 ± 2.29 ml/kg/h, respectively. After im administration (150 U/kg), mean bioavailability of ck was 51 ± 17% and maximal plasma ck activity (500 ± 97 U/L) was observed at 454 ± 131 minutes. The rate of ck activity entry into plasma was determined by use of deconvolution analysis. Two peaks were observed; the first appeared before the 30th minute after im administration, and the second appeared at 3.3 ± 1.1 hours. Amplitudes were 6.31 ± 4.45 and 6.57 ± 3.08 U/kg/h, for the first and the second peaks, respectively. The quantity of ck liberated from control muscle was 0.69 ± 0.12 U/kg/h, corresponding to a normal daily catabolism of 5.8 ± 1.0 mg of muscle/kg. From these results, the following equation can be proposed to determine the corresponding mean equivalent of destroyed muscle (Qmuscle, test article) after im administration of a test article:

Qmuscle, test article (g/kg) = 4.41 · 10-6. auc (U/h/L), with auc being the ck plasma activity area under the curve.

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