DISPOSITION OF CREATINE-KINASE ACTIVITY IN DOG PLASMA FOLLOWING INTRAVENOUS AND INTRAMUSCULAR INJECTION OF SKELETAL-MUSCLE HOMOGENATES

The fate of skeletal muscle-derived creatine kinase (CK) was investiga ted in six dogs. After i.m. and i.v. injections of 3000 g and 105 000 g supernatants of dog muscle homogenates, plasma CK activity was measu red up to 48 h. There was no significant difference in pharmacokinetic parameters dependent on the type of supernatant injected. After i.v. injection, the volume of distribution of CK was equal to the plasma vo lume, CK clearance was relatively low (about 0.5 mL/kg/min) and its te rminal half-life of elimination was about 2.5 h. After i.m. injection, the CK terminal half-life was about 6.5 h, demonstrating a flip-flop mechanism, i.e. a limiting absorption process from the site of injecti on. Bioavailability after i.m. injection was about 65%, and the rate o f absorption from muscle injection site was relatively slow: peak acti vity occurred at the second hour post administration, and most CK acti vity had been absorbed by 24 h. These pharmacokinetic parameters can b e used as a basis for a minimally invasive means of quantitating muscl e damage either after intramuscular drug administration or in canine s ports medicine.