In vivo metabolism and mass balance of 4-[4-fluorophenoxy]benzaldehyde semicarbazone in rats

The pharmacokinetics, mass balance, tissue distribution, and metabolism of Co 102862 was investigated in rats after a single oral dose. [C-14]Co 10286 2 showed multiexponential pharmacokinetics in rat plasma with an extensive distribution phase. After p.o. administration (similar to 10 mg/kg), the ha lf-lives were long for total radioactivity compared with unchanged Co 10286 2. Profiles of rat urine and bile suggest that Co 102862 is extensively met abolized in vivo. [C-14] Co 102862 was extensively distributed into all tis sues, with the fatty tissues and secretory glands tissues containing the hi ghest radioactivity. Elimination of radioactivity from the tissues had an e stimated half-life of 14 days. A total of 91% of the administered radioacti vity was recovered in both intact and bile-duct cannulated rats over 120 an d 48 h, respectively, with the majority (similar to 74%) of the radioactivi ty being excreted in the urine. Approximately 10% of the total radioactivit y remained in the tissues on day 5 and decreased with time to similar to 3% on day 28. Bile-duct cannulated experiments show the enterohepatic circula tion is an important route of elimination and reabsorption. Six metabolites were identified in the urine and bile of which the carboxylic acid was the major metabolite. The carboxylic acid was the only metabolite found in pla sma and was probably responsible for the radioactivity in the tissues.