Continuous Intravenous Infusion Study of 15-Deoxyspergualin HC1 (NSC-356894) in Beagle Dogs

摘要

15-deoxyspergualin HCl (NSC-356894), was given to dogs intravenously as a single dose or 120-hour continuous infusion dose. Plasma elimination was first order and dose-independent. Peak plasma concentrations were 90.8, 48.6, and 19.3 micrograms/ml for the dogs in the 256.0, 128.0, or 64.0 mg/sq. m. groups, respectively. Mean steady state plasma levels were 35.7, 21.9, or 7.2 microgram/ml for dogs in the 10.0, 6.0, or 2.0 mg/kg/hr groups, respectively. Mortality occurred for dogs in the 10.0 and 6.0 mg/kg/hr groups. Drug-related clinical observations were polyuria, bloody urine, emesis, bloody mucoid stool, diarrhea, no stool, ptyalism, low food consumptions, and lower body weights prior to death or sacrifice which were accompanied by changes in relative weights of the adrenal, brain, ventricles, kidney, liver, pituitary gland, and thyroid.