Volumes of Distribution and Clearances of Intravenously Injected Creatinine in the Dog 1

N A RECENT study it was reported by GreenI berg ef al. (I) that the volume of distribution of creatinine in the dog was of the order of 40-60% of the body weight (average 48.5 % ; range 37.9-59.7 %). This estimate was made by dividing the equilibrium concentration of exogenous creatinine in the plasma at the end of a constant infusion into the exogenous creatinine balance in the body fluids. The latter was estimated by determining creatinine excretion after discontinuing the infusion and subtracting the ‘dead space’ creatinine and basal creatinine excretion. The crea tinine space obtained was considerably lower than that previously reported for the volume of distribution of creatinine in the dog by Dominguez, Goldblatt and Pomerene (2). These authors, studying the disappearance curve of creatinine after single intravenous injection estimated the volume of distribution of creatinine to be 76% of the body weight, a value which they recognized to be greater than the body water. In their analysis of the disappearance curve of creatinine, Dominguez et ~2. originally made the basic assumption that with the passage of time creatinine became homogeneously distributed throughout its entire volume of distribution; that is to say, that the ‘tissue’ creatinine concentration became identical with the ‘plasma’ concentration after sufficient time had elapsed. That this assumption is invalid for two compartment systems with excretory and intercompartmen tal clearances can be demonstrated readily with physical models. It has also been shown (3) that after single intravenous injections of inulin in dogs