PHARMACOKINETIC VARIABLES AND BIOAVAILABILITY FROM MUSCLE OF CREATINE-KINASE IN CATTLE

Pharmacokinetic variables of skeletal muscle creatine kinase (CK) acti vity after rv administration of a muscle extract; CK bioavailability a fter IM administration of the muscle extract; and effect of IM adminis tration of saline solution, to appreciate the possible release of CK c onsecutive to muscle puncture, were determined in 6 cows. A general eq uation for the quantitative estimation of skeletal muscle damage also was derived. Administration of saline solution IM had no effect on pla sma CK activity (ANOVA, P > 0.05) in any of the cows. After IV adminis tration of the muscle extract (150 U/kg of body weight), mean volume o f the central compartment, plasma half-life, and plasma clearance of C K 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 bioavail ability of CK was 51 +/- 17% and maximal plasma CK activity (500 +/- 9 7 U/L) was observed at 454 +/- 131 minutes. The rate of CK activity en try into plasma was determined by use of deconvolution analysis. Two p eaks were observed; the first appeared before the 30th minute after IM administration, and the second appeared at 3.3 +/- 1.1 hours, Amplitu des 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 cata bolism of 5.8 +/- 1.0 mg of muscle/kg, From these results, the followi ng equation can be proposed to determine the corresponding mean equiva lent of destroyed muscle (Q(muscle, test article)) after IM administra tion of a test article: Q(muscle, test article) (g/kg) = 4.41 . 10(-6) AUC (U/h/L), with AUC being the CK plasma activity area under the cur ve.