Morisada S, Yanagi Y, Kashiwazaki Y, Fukui M
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka.
Jpn J Cancer Res. 1989 Jan;80(1):77-82. doi: 10.1111/j.1349-7006.1989.tb02248.x.
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.
在小鼠静脉推注后评估了SM - 5887的毒理学特征，并与阿霉素（ADR）的毒理学特征进行了比较。给予SM - 5887后观察到的急性毒性体征包括体重减轻、共济失调、脱发和骨髓抑制。它们在性质上与ADR诱导的体征相当。给药后14天观察确定的50%致死剂量值，在四种品系小鼠中，SM - 5887为32至50mg/kg，ADR为16至超过20mg/kg。估计SM - 5887的最大耐受剂量（MTD）为25mg/kg，ADR为12.5mg/kg（未发生死亡或体重减轻超过3g）。当对14天存活者给药后进一步观察至90天时，ADR在剂量超过10mg/kg时频繁且与剂量无关地表现出迟发性致死毒性，而SM - 5887则未出现。即使在MTD的一半剂量下，SM - 5887的骨髓抑制也比ADR在MTD时更严重，但其恢复比ADR后更快。此外，当将药物注射到小鼠后爪的足底区域时，ADR诱导严重的炎症反应，而SM - 5887仅产生轻微的炎症反应。数据表明，SM - 5887的毒性作用比ADR更具可逆性和可控性。
