Tissue tolerance of intramuscular injectables and plasma enzyme activities in rats.

The local tissue damage after intramuscular injection caused by various commercially available injection solutions was determined in the albino rat, by measuring plasma activities of creatine phosphokinase, aspartate aminotransferase, and lactic dehydrogenase, the tissue activity of creatine phosphokinase, and macroscopic changes in the muscle at the injection site (gastrocnemius muscle). The plasma enzyme activities were determined 2, 6, 18, and 28 hr after the injection. After 28 hr the animals were sacrificed for macroscopic inspection of the injection site and for the determination of tissue enzyme activity. The tissue injury caused by the test substances correlated well with the elevated creatine phosphokinase activity (2 hr). The elevations of aspartate aminotransferase (18 hr) and lactate dehydrogenase (2 hr) activity as well as the loss of tissue creatine phosphokinase activity were less indicative of differences between test preparations. The i.p. administration of some of the test preparations caused increased enzyme activity without muscle damage, which could interfere with the test results. The creatine phosphokinase determination indicates the damage occurring immediately after the administration of the test solution, and the macroscopic inspection offers the possibility to obtain some information on the evolution of the muscular lesion.