METABOLISM OF XILOBAM IN LABORATORY-ANIMALS AND MAN

1. Biotransformation and excretion of xilobam (Xm) were studied after single oral doses of Xm-C-14 in mouse, rat, dog and man. 2. Following oral administration of Xm-C-14, recoveries of total C-14 (0-24 h) in u rine were greater than or equal to 78% of the dose in all species. 3. Xm and a total of 11 metabolites have been isolated and identified, wh ich accounted for 30, 65, 21 and 49% of the total C-14 in the urine sa mples from mouse, rat, dog and man, respectively. 4. Xm was sequential ly oxidized at the pyrrolidine ring to form 5'-OH Xm and 5'-oxo Xm. Bo th metabolites were isolated from human plasma accounting for 61% of t he radioactivity in the sample. 5'-OH Xm was also identified as a majo r in vitro metabolite in the 9000g supernatant from a rat liver homoge nate preparation. 5. 5'-OH Xm was isolated from the urine of all speci es except rats. However, oxidation products of 5'-oxo Xm were also pre sent. Oxidation at the phenyl (ph) ring and at the phCH(3) group produ ced the corresponding 4-OHph and phCH(2)OH metabolites. Subsequent wat er addition at the 2-position of the pyrrolidine ring followed by clea vage and/or cyclization of the above metabolites resulted in six addit ional urinary metabolites.