Tests for local toxicity of intramuscular drug preparations: comparison of in vivo and in vitro methods

Different concentrations of aqueous preparations of metoclopramide, gaboxadol, cis(Z)-clopenthixol, digoxin and chlorpromazine and of cis(Z)-clopenthixol acetate in Viscoleo have been tested for local toxicity after intramuscular injection in rabbits. The weight of the areas of necrotic muscle tissue isolated 3 days after injection was determined In addition homogenized injection site muscle tissue was analysed for creatine kinase (CK) activity and by comparison with the activity of contralateral muscle tissue, the amount of injection site muscle tissue totally depleted for CK was calculated. The substances have also been tested for in vitro toxicity. The concentrations of the substances which caused 100% hemolysis of human erythrocytes or minimal cytotoxicity in cell culture assays using MRC-5 fibroblasts were estimated.