CARDIOTOXICITY OF A NEW ANTHRACYCLINE DERIVATIVE (SM-5887) FOLLOWING INTRAVENOUS ADMINISTRATION TO RABBITS - COMPARATIVE-STUDY WITH DOXORUBICIN

The degree of cardiotoxicity of SM-5887 compared with that of doxorubi cin was investigated in rabbits. Two experimental groups were administ ered high and low doses of SM-5887, respectively. One group was admini stered doxorubicin and another group was administered the vehicle only were prepared as positive and negative controls, respectively. Drugs were intravenously administered 3 times a week for 8 weeks. At terminu s, electrocardiograms were recorded under anesthesia. The blood was co llected for haematology and blood biochemistry analyses. Myocardial ti ssue damage was evaluated using light and electron microscopy. In the electrocardiogram study, prolongation of QTc interval and ST-T change were observed in rabbits administered SM-5887 and doxorubicin. Morphol ogical studies showed that myocardial tissue damage in animals adminis tered SM-5887 was comparable to that in the negative controls, and les s than that observed in the positive contros. The general toxicologica l investigations uniformly indicated lower toxicity in the SM-5887 gro up than in the doxorubicin group at equivalent dosages. In total, cons idering the results of antitumor efficacy studies comparing SM-5887 wi th doxorubicin, these results indicate that the cardiotoxicity of SM-5 887 is very slight, and that the general toxicity of SM-5887 is lower than that of doxorubicin.