Picolinaldehyde, 5 - Hydroxy - Thiosemicarbazone, (Nsc-107 392): Determination of Toxicity in Dogs

摘要

For determination of MTD, dogs (2 per dose level) were treated for 5 consecutive days with 43.5, 21.75, 10.8 or 5.2 mg/kg of Picolinaldehyde (Table 1). No mortalities occurred in this study. To prevent Picolinaldehyde - induced emesis, two dogs treated at the highest dose (43.5 mg/kg/day) were pretreated with Chlorpromazine 8 mg/kg or 4 mg/kg respectively 45 minutes prior to each Picolinaldehyde injection. Both doses of Chlorpromazine reduced the incidence of emesis approximately 50% from that of dogs treated with the same Picolinaldehyde dose but receiving no Chlorpromazine. Six dogs were not pretreated with Chlorpromazine. Two each received 21.75, 10.8 or 5.2 mg/kg of Picolinaldehyde. At these low doses, toxicity was not dose related. Predominant toxicity included leukopenia (5/6), vomiting (5/6), diarrhea (4/6), weight loss (5/6), anemia (3/6), and decreased serum Cl- (3/6). At least one animal at each dose level displayed toxic symptoms, but no consistent pathological changes were found at autopsy. Both dogs treated with 21.75 mg/kg showed bone marrow hypoplasia. The other 4 dogs exhibited no drug related pathology. Five consecutive daily I.V. injections with 5.2 mg/kg appeared to be acceptable as the MTD. (Author)