Toxicity Studies,Including Hemodynamic Effects,of Compound NSC 71795, Ellipticine,Lot No. BVL 70-226-2,Following 15Minute I.V. Infusion in Beagle Dogs,

摘要

Beagle dogs were treated with Ellipticine by a 15minute intravenous infusion of the drug in dosages of 32, 18and 9mg/kg x 1; 18mg/kg/day x 4and 5; 9and 4.5mg/kg/day x 5;and with a two course dosage schedule of 4.5mg/kg/day x 5with a 9day interval between dosages. Toxic signs noted after the single doses of the drug included licking, salivation,nasal discharge, dyspnea,tachycardia,muscle tremors,convulsions, prostration,hyperthermia, catatonic sitting position,decrease in muscle tone,head drooping, puffiness about the eyes,decrease in erythroid elements,shift to the left in the WBC differentail, BSP retention,elevations in alkaline phosphatase and SGOT, prothrombin time and serum globulin with a decrease in A/G ratio and suggestive changes in electrolytes. Overt toxic signs for the most part were acute but residual signs were noted up through 4-6days at the highest dose and included ataxia and hind limb spread. When administered daily for 5days 18mg/kg/day was lethal and doses of 9mg/kg and 4.5mg/kg were toxic. Toxic signs noted included those enumerated above for the animals.