Dose-response relationships of chronic adriamycin toxicity in rabbits

Doxorubicin was administered chronically to 55 female New Zealand White rabbits in order to determine a chronic dose-response relationship for doxorubicin-induced cardiomyopathy, skeletal myopathy and nephropathy. Systolic time interval recording as a measure of cardiac function in doxorubicin-induced cardiomyopathy in the rabbit is compared to histologic grading of the cardiomyopathy. Histologic evidence of cardiomyopathy was not seen at cumulative doses less than 100 mg/m2 but incidence and severity of cardiomyopathy increased with increasing doxorubicin dosage. The most severe lesions were seen at cumulative doses in excess of 400 mg/m2. The dose-response of skeletal myopathy paralleled that of cardiomyopathy but the severity of histologic abnormalities and the incidence of skeletal myopathy was less than half that of cardiomyopathy at all dose levels. Nephropathy was a consistent finding at cumulative doses of doxorubicin in excess of 100 mg/m2.