Yakugaku Zasshi. 1991 Nov; 111(11): 687-94.

[Metabolic fate of bufalin and cinobufagin]

Toma S, Hirai Y, Sugimoto C, Shoji M, Oguni Y, Morishita S, Ito C, Horie M.

Research Laboratories of Kyushin Pharmaceutical Co., Ltd., Tokyo, Japan.

In the course of study of the metabolic fate of "Kyushin", a traditional medicine containing toad venom, the metabolic fates of bufalin and cinobufagin, main constituents of toad venom, have been studied. Six metabolites were detected in the extracts from incubation mixture of rat liver slice with bufalin, and one main metabolite shown by mass spectroscopy and high performance liquid chromatography (HPLC) to be 3 alpha-bufalin. Serum levels of bufalin and 3 alpha-bufalin were determined by HPLC after oral administration of 2000 micrograms/kg of bufalin, and both compounds appeared in the rat serum. On the other hand, only 3 alpha-bufalin appeared after administration of 20 or 200 micrograms/kg. 3 alpha-Bufalin levels increased dose dependently. Serum levels of cinobufagin and its metabolites and digitoxin were compared after repeated intravenous administration (5 h interval) of cinobufagin or digitoxin. Although digitoxin was accumulated in the rat serum, cinobufagin and its metabolites were not. Inhibitory activities of metabolites of bufalin and cinobufagin on (Na+ + K+)-adenosine triphosphatase were less than those of original compounds.