120-Hour Continuous Intravenous Infusion Study of NSC-D629243 Rats.

摘要

The study was conducted to determine the potential target organ toxicity and its reversibility in rats of NSC-D629243 in 70 percent DMSO after 120-hours of continuous intravenous infusion. The study consisted of four groups of rats, 3/sex/group. Drug was infused at two different rates. Groups 1 and 2 (0 and 0.9 mg/kg/hr, respectively) were infused at a rate of 0.1 mL/kg/hr, while Groups 3 and 4 (0 and 2.6 mg/kg/hr, respectively) were infused at 0.3 mL/kg/hr. On Study Day 8, all males were sacrificed and on Study Day 34 all females were sacrificed. All animals survived until scheduled termination. There were no discernible signs of toxicity related to the continuous intravenous infusion of NSC-D629243. All signs of abnormality were related to the vehicle (70 percent DMSO). Infusion of DMSO produced destruction of erythrocytes by intravascular hemolysis, with the high solute load of hemoglobin and cellular contents producing hematuria and a slight transient rise in urine specific gravity. The anemia arising from hemolysis was judged to be regenerative, normochromic, and macrocytic in nature. There were no obvious differences in the response to flow rates of 0.1 or 0.3 mL/kg/hr DMSO. There was no evidence of histopathologic abnormality related to DMSO or NSC-D629243. All such signs of toxicity related to DMSO were reversed in the post-treatment phase.