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.
Yakugaku Zasshi. 1991 Nov;111(11):687-94. doi: 10.1248/yakushi1947.111.11_687.
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.
在对含有蟾酥毒素的传统药物“救心”的代谢命运研究过程中，对蟾酥毒素的主要成分蟾毒灵和华蟾酥毒基的代谢命运进行了研究。在用蟾毒灵孵育大鼠肝切片的混合物提取物中检测到了六种代谢产物，通过质谱和高效液相色谱法（HPLC）显示一种主要代谢产物为3α-蟾毒灵。口服2000微克/千克蟾毒灵后，通过HPLC测定蟾毒灵和3α-蟾毒灵的血清水平，两种化合物均出现在大鼠血清中。另一方面，给予20或200微克/千克后仅出现3α-蟾毒灵。3α-蟾毒灵水平呈剂量依赖性增加。在重复静脉注射（间隔5小时）华蟾酥毒基或洋地黄毒苷后，比较了华蟾酥毒基及其代谢产物和洋地黄毒苷的血清水平。尽管洋地黄毒苷在大鼠血清中蓄积，但华蟾酥毒基及其代谢产物却没有。蟾毒灵和华蟾酥毒基的代谢产物对（Na + + K +）-三磷酸腺苷酶的抑制活性低于原始化合物。
