The metabolism of carfecillin in rat, dog and man

Abstract

1. The absorption of the phenol moiety of [phenol-¹⁴C]carfecillin following oral administration to rat, dog and man was extensive, since 95%, 73% and 99% of the administered radioactivity respectively was recovered in the urine. In contrast, less than half of the carbenicillin moiety of carfecillin was absorbed after oral administration, as judged by excretion studies using [carbenicillin-¹⁴C]carfecillin in intact and bile-duct cannulated animals.

2. The patterns of radiometabolites in the urines of rat, dog and man following single oral administration of [phenol-¹⁴C]carfecillin were determined by chromatography and radioassay. In two men, the majority of a dose was excreted as phenylsulphate (71%) and phenylglucuronide (16%) with the sulphate and glucuronic acid conjugates of quinol representing small amounts of the urinary radioactivity. Similar metabolic patterns were observed in the rat and dog following oral administration of either [¹⁴C]phenol or [phenol-¹⁴C]carfecillin, although some saturation of sulphate conjugation was apparent at the dose levels employed.