[Experimental studies on intravesical instillation of SM-5887, a novel anthracycline derivative for treatment of bladder carcinoma].

SM-5887 is a novel anthracycline derivative. Experimental studies of its intravesical chemotherapy were carried out to elucidate its histopathological effect on the normal bladder mucosa and the pharmacokinetics in Beagle dogs. Forty mg (4,000 micrograms/ml), 60 mg (6,000 micrograms/ml) and 80 mg (8,000 micrograms/ml) of SM-5887 dissolved in 10 ml of physiological saline were instilled into the empty bladders of dogs with bilateral cutaneous ureterostomy, respectively. SM-5887 instilled intravesically scarcely passed into the blood. In only one dog of five instilled with 80 mg of SM-5887 intravesically, the serum level of 0.0248 micrograms/ml was detected 2 hours after instillation, but all the others were below the detection limit (0.020 micrograms/ml). Excretion of SM-5887 into the urine was also low. The highest urinary excretion was observed 6 hours after instillation of 80 mg of SM-5887, yet the concentrations of SM-5887 and its metabolites in the urine were extremely low. The urinary concentrations of SM-5887 and its active metabolite, 13-OH derivative, were 0.029 micrograms/ml and 0.131 micrograms/ml, respectively. Other metabolites were not detected. The distribution of SM-5887 in the bladder mucosa and muscular layer was almost equal, but the concentration of its active metabolite, 13-OH derivative, was 5 to 10 times higher in the bladder mucosa than in the bladder muscular layer. The distributions of SM-5887 in the organs other than the bladder, that is, the cortex and medulla of kidney, heart, lung, liver, and spleen, were very low, and those of a 13-OH active metabolite were even lower. In addition, SM-5887 barely affected the normal bladder mucosa. In dogs instilled with 80 mg of SM-5887, no histological change was observed in the bladder mucosa and submucosal layer even after 6-hour retention at the highest concentration of 8,000 micrograms/ml.