Tests for local toxicity of intramuscular drug preparations. Comparison of in vivo and in vitro findings.
The local tissue tolerance after intramuscular injection caused by two multivitamin preparations, two excipient preparations without vitamins and a reference preparation (glycine 2.5%) was determined in albino rats and volunteers by measuring the creatine phosphokinase activity in the blood. The creatine phosphokinase activity was determined 2 h after the injection in the rats and before, 6, 12, 24, and 48 h after the injection in the volunteers. These measurements were compared to findings from an in vitro test using the haemolytic effect of the preparations in human erythrocytes. The haemolytic potential of the drug and excipient preparations was closely correlated to the creatine phosphokinase elevation in rats. The elevation of creatine phosphokinase in the volunteers was not indicative of any differences between the test preparations. Thus it could be shown that the elevation of the creatine phosphokinase activity is useful in demonstrating muscle damage and that the haemolytic potential of the drug and excipient preparations are closely related to the elevation of the creatine phosphokinase activity in rats. However, the results of the elevation of the creatine phosphokinase activity in humans are inconclusive for determining local muscle damage.
Surber
C
C
Pharmaceutical Research and Development, F. Hoffmann-La Roche & Co. AG, Basle, Switzerland.
Dubach
U C
UC
D000328:Adult; D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007273:Injections, Intramuscular / Q000009:adverse effects*; D008297:Male; D051381:Rats; D013045:Species Specificity
D003402:Creatine Kinase