Imondi A R
Battelle Memorial Institute, Columbus, OH 43201, USA.
Semin Oncol. 1998 Aug;25(4 Suppl 10):22-30.
The ability of dexrazoxane (DEX) to protect against doxorubicin (DOX)-induced cardiomyopathy has been demonstrated in mice, normotensive and hypertensive rats, rabbits, dogs, swine, and humans. These animal models of DOX-induced cardiomyopathy were found to be highly predictive of DEX activity clinically. In mice administered maximally tolerated doses of DOX over a period of 7 weeks, the optimum dose of DEX was from 10:1 to 20:1 (DEX:DOX) given from 30 minutes before to 15 minutes after DOX. The dose ratio required to reduce the incidence of moderate to severe cardiomyopathy by 90% in the mouse was more than 20:1 for DOX and 10:1, 5:1, and 5:1 for epirubicin, daunorubicin, and idarubicin, respectively. Dexrazoxane was most effective in rats when treatment commenced with the first and third doses of DOX, but also provided cardioprotection when started with the sixth of 10 doses of DOX. The cardioprotective activity of DEX in rats was evident for more than 6 months after completion of DOX dosing. Results of antitumor studies in several experimental tumor models indicate that DEX does not interfere with the antineoplastic activity of DOX or other antitumor drugs. In some case, especially cyclophosphamide, there was a markedly synergistic antitumor effect when combined with DEX.
在小鼠、正常血压和高血压大鼠、兔子、狗、猪及人类中，已证实右丙亚胺（DEX）可预防多柔比星（DOX）诱导的心肌病。这些DOX诱导的心肌病动物模型在临床上被发现对DEX活性具有高度预测性。在7周内给予最大耐受剂量DOX的小鼠中，DEX的最佳剂量为DOX给药前30分钟至给药后15分钟给予的10:1至20:1（DEX:DOX）。在小鼠中，将中度至重度心肌病的发生率降低90%所需的剂量比，DOX为20:1以上，表柔比星、柔红霉素和伊达比星分别为10:1、5:1和5:1。当从DOX的第一剂和第三剂开始治疗时，右丙亚胺在大鼠中最有效，但从10剂DOX的第六剂开始时也提供心脏保护作用。在DOX给药完成后，DEX在大鼠中的心脏保护活性在6个月以上都很明显。在几种实验性肿瘤模型中的抗肿瘤研究结果表明，DEX不会干扰DOX或其他抗肿瘤药物的抗肿瘤活性。在某些情况下，尤其是环磷酰胺，与DEX联合使用时具有明显的协同抗肿瘤作用。
