LONG-LASTING EFFECT OF DEXRAZOXANE AGAINST ANTHRACYCLINE CARDIOTOXICITY IN RATS

The long-lasting protective effect of dexrazoxane (ADR-529) against do xorubicin- and epirubicin-induced cardiotoxicity was evaluated in the multiple-dose 35-wk rat model. Groups of 36 male Sprague-Dawley rats w ere given ADR-529 30 min before administration of cardiotoxic doses of doxorubicin (1 mg/kg/wk) or epirubicin (1.13 mg/kg/wk). The compounds were intravenously injected once weekly for 7 consecutive wk at ADR-5 29: anthracycline ratios ranging from 5:1 to 20:1. These ratios covere d the entire chemotherapeutic range in humans and allowed studying the chronic progressive cardiomyopathy in our rat model. Animals were obs erved for up to 35 wk to follow the time course of the well-characteri zed cardiomyopathy, which was evaluated through the well-established q ualitative/quantitative morphological grading. It was clearly demonstr ated in this rat model that ADR-529, at the ratios administered, provi ded ample cardioprotection for a duration of 35 wk, which corresponds to 25 yr of equivalent human time.