NONINVASIVE AND QUANTITATIVE-EVALUATION OF POST-INJECTION MUSCLE DAMAGE BY PHARMACOKINETIC ANALYSIS OF CREATINE-KINASE RELEASE

Intramuscular administration of veterinary drugs can induce severe mus cle damage resulting in economic losses and residue persistence. Local tolerance is usually evaluated by macroscopic examination of the inje ction site requiring euthanasia of a large number of animals. A noninv asive quantitative method, based on the pharmacokinetic analysis of cr eatine kinase (CK) release from muscle, is proposed for the evaluation of post-injection muscle damage. Plasma CK activity is a specific and sensitive marker of skeletal muscle damage. Three disposition paramet ers are needed to measure the actual amount of CK released by the inju red muscle: plasma CK clearance, bioavailability of CK from muscle and area under the plasma CK activity vs time curve. A CK solution from a homologous muscle extract was administered in different animal specie s by intravenous route and by intramuscular route for the determinatio n of the CK disposition parameters. The general equation for the deter mination of the destroyed muscle equivalent (Q), following the drug in tramuscular injection, is: Q = CI x AUC / F x M, with CI, the plasma C K clearance; AUC, the area under the plasma CK vs time curve after dru g administration; F, the CK bioavailability from muscle; and M, the CK content in the injected muscle. Population equations are proposed for dogs, sheep, horses and cattle and their use is illustrated. Rabbits and pigs seem inappropriate species for the pharmacokinetic approach b ecause of stress-induced spontaneous increases in plasma CK. In cattle , for example, a (g.kg(-1) body weight) = 4.4 x 10(-6) AUC (U.h.L(-1)) and the estimated equivalent of muscle destroyed after a single IM in jection of a chloramphenicol formulation was about 300 g. This screeni ng approach is simple, ethical, rapid and inexpensive.