抄録
Degradation of four benzodiazepines, i.e. bromazepam, diazepam, desmethyldiazepam, and 7-bromo-1, 3-dihydro-5-phenyl-2H-1, 4-benzodiazepin-2 (1H) -one, in a broth containing human feces was studied. Degradation of bromazepam was also investigated in a fecal medium, a homogenate of the liver and a homogenate of intestinal epithelial cells of rat. More than 80% of bromazepam, which contains a pyridine ring in its structure, was degraded in the broth containing 8% human feces under both anaerobic and aerobic conditions. The major degradation product of bromazepam was identified as 2- (2-amino-5-bromobenzoyl) pyridine by means of thin layer chromatography and gas chromatography-mass spectra analyses. About 70, 90, and 90% of bromazepam remained in the fecal medium, homogenate of the liver and homogenate of intestinal epithelial cells of rat, respectively, after incubation for 5 h at 37 °C.
Therefore, degradation of bromazepam by the intestinal microflora may be considered to be one of the major factors influencing the bioavailability after oral administration to man.
