Metabolism of creatinine in vivo.

Two forms of radiolabeled creatinine were used in this study, [carbonyl-14C]- and [amidino-14C]creatinine, the latter being synthesized in this laboratory. These labeled compounds were given intravenously to rabbits. Specimens of plasma, urine, feces, and selected tissues were collected. These were liquid-chromatographed and the separated components compared for radioactivity and identity. This first use of amidino-labeled creatinine revealed the metabolic conversion of small amounts of creatinine to an unidentified non-basic compound and guanidinobutyrate in normal rabbits and to guanidinopropionic acid and arginine in a rabbit that had a low creatinine clearance. A mechanism is suggested for this metabolic process. The proposed pathway may be a major route of elimination of creatinine in renal failure.