[Toxicity, pharmacokinetics and pharmacodynamics of Soviet-made doxorubicin].

The LD50 of doxorubicin, prepared at the Institute of New Antibiotics of the Academy of Medical Sciences of the USSR was 4.6, 12.5, 13.5 and 570 mg/kg for single intraperitoneal, intravenous, subcutaneous and oral administrations to albino mice, respectively. When used intravenously in a single dose, it had an inhibitory effect on the blood system of albino mice and rats. The cumulative properties of doxorubicin were somewhat higher than those of rubomycin or carminomycin. At an average 30 and 96 per cent of doxorubicin were bound with the proteins of rabbit blood serum and the organ homogenates, respectively. The antibiotic levels in organs were high and persisted for prolonged periods. About 10 and 13 per cent of doxorubicin were excreted with 24 hours with urine and bile, respectively. In doses close to the therapeutic ones (1 mg/kg) doxorubicin had no significant effect on the arterial pressure and respiration of anesthetized cats. a 5--10-fold increase of the dose resulted in a marked decrease of the arterial pressure and in excitation of the respiration. The amplitude of the ECG did not change significantly. The effect of doxorubicin on the heart rate was inconclusive.