1. The parenteral toxicity of clindamycin 2-phosphate in laboratory animals
- Author
-
R.N. Weaver, Ernest S. Feenstra, J. Moran, and Jack E. Gray
- Subjects
medicine.medical_specialty ,Injections, Subcutaneous ,Administration, Oral ,Toxicology ,Hemolysis ,Injections, Intramuscular ,Beagle ,Phosphates ,Transaminase ,Lethal Dose 50 ,Lesion ,Mice ,Dogs ,New Zealand white rabbit ,Internal medicine ,medicine ,Animals ,Aspartate Aminotransferases ,Creatine Kinase ,Inflammation ,Pharmacology ,Dose-Response Relationship, Drug ,Staining and Labeling ,biology ,Clindamycin Hydrochloride ,Chemistry ,Clindamycin ,Muscles ,Body Weight ,Erythrocyte fragility ,Alanine Transaminase ,biology.organism_classification ,Rats ,Microscopy, Electron ,Endocrinology ,Liver ,Anesthesia ,Injections, Intravenous ,Toxicity ,Rabbits ,medicine.symptom ,medicine.drug - Abstract
The ip and iv LD50 values of 1145 and 855 mg/kg of clindamycin 2-phosphate in the Swiss white mouse were approximately 3 times higher than those of clindamycin hydrochloride. The lesion produced by single injection of 50 or 100 mg/ml of clindamycin 2-phosphate in the loin muscles of the New Zealand White rabbit was graded as slight. The 24-hr serum creatine phosphokinase value was 1500 IU/liter which was less than one-half that of the parent antibiotic. Body weight gains and food conversion ratios in groups of 10 Sprague-Dawley rats injected sc with 120 mg/kg for 6 days were comparable to those of the control group; 90 mg/kg was tolerated in these terms nearly as well for 30 days as no treatment or doses of 30 and 60 mg/kg. From 22 to 33 injections (each equivalent to 30, 60 or 90 mg/kg) were made bilaterally in the posterior thigh muscles of groups of 3 beagle dogs. The terminal elevations of serum glutamic-oxaloacetic transaminase varied from 54 to 400 Reitman-Frankel units. The characteristic pathologic change resulting from the superimposed injections was dose-related progressive scarring of the muscle bundles. Intravenous administration of 60 and 120 mg/kg daily in divided doses in 2 groups of 4 dogs each for 30 days produced no detectable irritation in the peripheral veins or drug-related hemolysis. Tests for drug-induced hemolysis and changes in erythrocyte fragility by in vitro methods were negative. In dogs treated iv with 120 mg/kg for 1 week, as light increase in neutral lipid droplets was present in hepatocytes from 3 hr to 3 days when examined by electron microscopy. This transient change was not observed in dogs injected im with 90 mg/kg for the same period.
- Published
- 1974