An in vitro model for assessing muscle irritation due to parenteral antibiotics

A rat skeletal muscle cell line (L6) was evaluated for its potential to discriminate the muscle-irritating liability of several parenteral antibiotics. The cells were exposed to clinical as well as diluted concentrations of tetracycline, cefoxitin, cephalothin, carbenicillin, erythromycin, ceforanide, cefazolin, and cephaloridine for 1 hr. Control cells were similarly exposed to culture media for 1 hr. The cells were subsequently assayed for their content of the muscle-associated enzyme creatine kinase (CK). Depletion of CK relative to control cultures was utilized as the index of cellular damage. The results of these analyses revealed the following ranking of antibiotic toxicity to L6 muscle cells: tetracycline, erythromycin, cefoxitin greater than cephalothin, carbenicillin greater than ceforanide, cefazolin greater than cephaloridine. The relative order of toxicity of these antibiotics to L6 cells is in good agreement with their reported muscle-irritating liability in man. The correlation between the results obtained in vitro and the irritancy data in vivo suggests that this model may be a useful adjunct to in vivo testing of parenteral antibiotics for muscle-irritation liability.