Pharmacokinetics and Dose Range-Finding of Cyclodisone (NSC-348948) in Beagle Dogs (Task 05)

摘要

Dogs tolerated single oral doses of 15 and 30 mg/kg of cyclodisone. A small decrease in body temperature was noted during the first three hours post dosing. Drug-related clinical signs of toxicity including hyperactivity, salivation and emesis were noted in 1 to 4 dogs on Days 1 and/or 2. The differential leukocyte count noted for the 30 mg/kg female dog on Day 8 showed a marked decrease in segmented neutrophils and a slight increase in eosinophils. Serum chemistries indicated that the liver was a target organ for cyclodisone-induced toxicity with increases in serum alkaline phosphatase, ALT and AST, decreases in glucose values in 3/4 dogs and with increases in prothrombin time in 1/4 dogs. The marked increases seen in serum ALT and AST in the two female dogs and the substantial increase in prothrombin time in one of these female dogs indicate that female dogs appear to be more sensitive to the toxic effects of cyclodisone than male dogs.