STUDIES ON ANTIBILHARZIAL DRUGS ⅩⅪ.TOXICITY AND THERAPEUTIC ACTIVITY OF Sb-58,Sb-126 AND TWSb AND THE DISTRIBUTION AND EXCRETION OF ANTIMONY AFTER ADMINISTRATION OF THESE COMPOUNDS

Dogs received intramuscularly 6 injections each of Sb-58,Sb-126 and TWSb.They caused slight irritation locally,but exerted little influence on blood sugar and electrocardiogram.Food intake decreased in all,more pronounced with TWSb,which produced a damage to heart and liver more seriously than the other 2 drugs. Dogs,previously infected with Schistosoma japonicum,were treated i.m.with Sb-58,Sb-126 and TWSb.The dosages were respectively 6,3 and 6 mg/kg b.i.d.for 3 days.The blood Sb concentrations 1/2 hour after the last injection were 5.0,4.1 and 6.5 μg/5 ml respectively,and all dropped to about 2 μg after 24 hours.The dogs were killed after a holding period of 13 days,and the average numbers of worms remained in each dog were found to be 60,16 and 67 respectively.Sb-126 caused the highest degree of degeneration of the helminths and a com- plete cure of 1 dog.Hence,the therapeutic activity of Sb-126 was deemed to be slightly higher. Infected rabbits were given i.m.1 injection each of the 3 antimonials at an equivalent dosage of 2.92 Sb mg/kg.The blood Sb level 1/2 hour later was lowest for Sb-126 (5μg/5 ml)and highest for TWSb(21 μg/5 ml).After 24 hours,the blood Sb levels all lowered to about 1 μg.No marked difference among the 3 drugs with respect to the Sb concentrations was observed in liver,kidney,spleen and schistosomes.The urinary excretion of Sb in 24 hours was greatest for TWSb(40%)and least for Sb-126(25%).It was believed that the slower excretion of Sb-126 was partly responsible for its higher therapeutic efficacy.