Mormont M C, von Roemeling R, Sothern R B, Berestka J S, Langevin T R, Wick M, Hrushesky W J
Department of Medicine, University of Minnesota, Minneapolis 55455.
Invest New Drugs. 1988 Dec;6(4):273-83. doi: 10.1007/BF00173645.
Compared to doxorubicin, equimolar epirubicin toxicity is reduced by about 50% by the epimerization of a hydrogen and hydroxyl group at the 4' position of the anthracycline sugar moiety. The circadian timing of doxorubicin administration markedly affects its lethal and sub-lethal bone marrow and gut toxicities in mice, as well as the severity of its clinical toxicity. We tested whether the timing of administration of equitoxic epirubicin doses similarly affected the toxicological response in female CD2F1 mice. A large and highly reproducible effect of the circadian stage of administration was documented with best drug tolerance occurring during the first half of the daily rest (light) span of the animals. In addition to this circadian rhythm, a significant seasonal effect was found with significantly fewer deaths occurring after epirubicin was given in the Summer, as compared to the Winter. Safest circadian timing for epirubicin is statistically significantly earlier in the day than for doxorubicin, while their seasonal patterns are quite similar.
与多柔比星相比，通过蒽环类糖部分4'位上氢和羟基的差向异构化，等摩尔表柔比星的毒性降低了约50%。多柔比星给药的昼夜节律显著影响其对小鼠致死和亚致死性骨髓及肠道的毒性，以及其临床毒性的严重程度。我们测试了等毒性表柔比星剂量的给药时间是否同样会影响雌性CD2F1小鼠的毒理学反应。给药昼夜阶段具有大且高度可重复的效应，在动物每日休息（光照）期的前半段给予药物时耐受性最佳。除了这种昼夜节律外，还发现了显著的季节效应，与冬季相比，夏季给予表柔比星后死亡的小鼠明显减少。表柔比星最安全的昼夜给药时间在统计学上比多柔比星显著更早，而它们的季节模式相当相似。
