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

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Abstract
Equations were derived for the analysis of the disappearance curve of an injected material from a 2 compartment system, one compartment of which eliminates the injected material to the outside at a rate proportional to its existing concentration and transfers it to the 2d compartment at a rate proportional to the existing concentration difference between the 1st and 2d compartments. The disappearance curves predicted from these equations are double exponential curves. Formulas are given for converting the intercepts and slopes of such double exponential curves into values for the excretory and intercompartmental clearances and the 1st and 2d volumes of distribution. The disappearance curve of creatinine corresponded to a double exponential process in 9 of 10 experiments in dogs. The creatinine clearance calculated from the creatinine disappearance curve was in good agreement with the mannitol clearance simultaneously determined. The volume of rapid distribution of creatinine corresponded roughly to the mannitol space (extracellular fluid) but may not always yield a valid measure of a true anatomical space. The intercompartmental clearance ranged from 100-359 ml/minute. The total volume of creatinine distribution was 36.8% of the body weight, a figure considerably smaller than any previously reported. Reasons for the discrepancy are discussed.

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