Task 2 Preclinical Single and Five Daily Dose Range-Finding and Lethality Studies of Azacitidine (NSC-102816) in CD2F1 Mice

摘要

Single and Five Daily Dose Lethality Studies in Mice. Groups of CD2F1 mice were administered graded doses of Azacitidine (NSC-102816) by intravenous injection (Single Dose Study and Five Daily Dose Study). The final LD90, LD50, and LD10 respectively, are as follows. Single Dose Male: 439.3, 300.4, 205.4 mg/kg (1317.9, 901.2, 616.2 mg/sq. m.). Single Dose Female: 288.1, 228.9, 181.9 mg/kg (864.3, 686.7, 545.7 mg/sq. m.). Single Dose Combined Sexes: 313.0, 249.8, 199.4 mg/kg (939.0, 749.4, 598.2 mg/sq. m.). Five Daily Dose Male: 15.60, 13.31, 11.35 mg/kg/day (46.80, 39.93, 34.05 mg/sq. m./day). Five Daily Dose Female: 13.87, 12.58, 11.41 mg/kg/day (41.61, 37.74, 34.23 mg/sq. m./day). Five Daily Dose Combined Sexes: 14.80, 12.91, 11.26 mg/kg/day (44.40, 38.73, 33.78 mg/sq. m./day). The major pharmacotoxic signs were hypoactivity, emaciation, high carriage (hunched back), and death. There was mild to moderate weight loss in treated animals that was dose-related and reversible by termination of the studies.