An in vitro model to evaluate muscle damage following intramuscular injections.
An isolated rat muscle preparation was developed to screen for muscle damage (myotoxic potential) following intramuscular injections. Myotoxicity is evaluated by the total cumulative efflux of the enzyme creatine kinase from the extensor digitorum longus muscle into the incubation medium over a 2-hr period or by the slope of the cumulative creatine kinase efflux curve. The system allows for rapid screening of compounds and/or formulations regarding their myotoxic potential and is not sensitive to fluctuations of in vivo creatine kinase levels caused by animal handling or patient conditions. A good rank-order correlation was obtained between this in vitro technique and the in vivo myotoxicity of a number of pharmaceutical formulations, as indicated by circulating creatine kinase levels and histological observations.
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo 14260.
G A
GA
Brazeau
H L
HL
Fung
D000818:Animals; D004796:Clinical Enzyme Tests; D003402:Creatine Kinase / Q000378:metabolism*; D064420:Drug-Related Side Effects and Adverse Reactions; D066298:In Vitro Techniques; D007273:Injections, Intramuscular; D008297:Male; D008954:Models, Biological; D009132:Muscles / Q000187:drug effects* / Q000201:enzymology; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains
D004364:Pharmaceutical Preparations; D003402:Creatine Kinase