Toxicological aspects of a novel 9-aminoanthracycline, SM-5887.
The toxicological characteristics of SM-5887 were evaluated in mice after a bolus intravenous injection, and compared with those of adriamycin (ADR). The acute toxic signs observed after SM-5887 administration were body weight decrease, ataxia, hair loss, and myelosuppression. They were qualitatively comparable to those induced by ADR. The 50% lethal dose values determined by 14-day observation after drug administration were in the range of 32 to 50 mg/kg for SM-5887 and 16 to more than 20 mg/kg for ADR in four strains of mice. The maximum tolerated doses (MTD) were estimated to be 25 mg/kg for SM-5887 and 12.5 mg/kg for ADR (no death or body weight loss of more than 3 g occurred). When 14-day survivors were further observed until 90 days after drug administration, ADR frequently and dose-independently showed delayed-type lethal toxicity at doses of more than 10 mg/kg, whereas SM-5887 did not. The myelosuppression of SM-5887 was more severe even at a half of the MTD than that of ADR at the MTD, but its recovery was more rapid than that after ADR. In addition, when the drugs were injected into the subplantar region of mouse hind paws, ADR induced a severe inflammatory reaction, whereas SM-5887 yielded only a slight one. The data suggest that toxic effects of SM-5887 are more reversible and more controllable than those of ADR.
Morisada
S
S
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka.
Yanagi
Y
Y
Kashiwazaki
Y
Y
Fukui
M
M
D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004317:Doxorubicin; C055866:amrubicin