The L6 muscle cell line as a tool to evaluate parenteral products for irritation.
A rat skeletal muscle cell line (L6) was evaluated for its utility in assessing cellular damage caused by parenteral administration of eight commercially available pharmaceuticals. The physical forms of the eight pharmaceuticals were diverse, including aqueous and non-aqueous suspensions and solutions. The L6 cells were exposed to therapeutic as well as diluted concentrations of methocarbamol, lorazepam, dimercaprol, phytonadione, menadiol sodium phosphate, penicillin G procaine, penicillin G benzathine, and iron dextran complex. Irritation assessment was based on the depletion of creatine phosphokinase (CK) from treated cultures versus untreated controls. The results obtained correlate well with reports of irritation and side effects noted in clinical use, and demonstrate the versatility of the model for testing suspensions and non-aqueous parenteral solutions. The L6 model is a useful tool to assist in determining the relative local irritancy of parenteral products.
Laska
D A
DA
Toxicology Division, Lilly Research Laboratories, Greenfield, IN 46140.
Williams
P D
PD
Reboulet
J T
JT
Morris
R M
RM
D000818:Animals; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D003402:Creatine Kinase / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D006863:Hydrogen-Ion Concentration; D007263:Infusions, Parenteral; D009132:Muscles / Q000187:drug effects* / Q000201:enzymology; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D051381:Rats
D004364:Pharmaceutical Preparations; D003402:Creatine Kinase