1976 年 96 巻 7 号 p. 819-826
Absorption, excretion, distribution, and metabolism of 2-(5H- benzopyrano [2, 3-b] pyridin-7-yl) propionic acid (Y-8004), a new anti-inflammatory agent, were investigated in rats and mice by the use of 14C-labeled compound (14C-Y-8004). When the radioactive compound was given to rats orally or intraperitoneally, about 50% of the given radio-activity (14C) was excreted in urine and 40% in feces during 72 hr, while about 80% in urine and 20% in feces after oral administration to mice. Approximately 55-60% was recovered in rat bile during 24 hr after oral administration. The highest blood level of 14C was obtained at 0.5-1 hr after oral administration to rats and mice. A good correlation was observed between blood level and dose level. However, apparent species difference in the blood 14C concentration and its disappearance rate were observed between rats and mice. When 14C-Y-8004 was orally administered to bileduct-cannulated rat, the blood 14C concentration and its disappearance rate came close to those of normal mice. The highest concentration of 14C was observed in the serum and relatively high levels in the liver and kidney of rats and mice after oral administration of 14C-Y-8004. In both animals, most of 14C in the serum existed as unchanged material bound to serum protein. Thin-layer chromatography after enzymic, acid, and alkaline hydrolysis experiments showed that the major metabolite in urine and bile of rats was Y-8004 acylglucuronide and in urine of mice Y-8004 acylglucoside. The present investigation provides the first evidence for the formation of an acylglucoside of a drug in mammals.