The volumes of distribution of a number of substances of widely varying molecular size and chemical properties, including sulfate, thiosulfate, mannitol, sucrose, and inulin, have been found to represent 15 to 25 per cent of body weight of man, dog, and other mammals. The apparently equal volumes of distribution of these dissimilar substances has suggested that the distribution of each of these substances measures the same portion of body fluid and has led to efforts to identify this volume of body fluid with the extracellular fluid volume.In a series of individuals, however, there is a considerable range in the fraction of body weight which the volume of distribution of any one of these substances represents. In only a few instances have the distributions of two of these substances been compared simultaneously in the same individual. Schwartz (1) reported a ratio of thiosulfate volume to simultaneously measured mannitol volume of 0.90 (0.87 to 0.96) in four normal dogs, a ratio of 1.02 and 0.98 in two normal human subjects, and a ratio of inulin to simultaneously measured mannitol volume of 0.97 (0.93 to 1.02) in six normal human subjects (2). Walser, Seldin, and Grollman (3) (7) found that the ratio of inulin volume to thiosulfate volume averages 0.79 in five nephrectomized dogs.To determine which, if any, of these substances distribute in equal volumes, the distributions of six substances: radiosulfate, thiosulfate, mannitol, sucrose, raffinose, and inulin, ranging in molecular weight from 96 to 5100 and including two anions, have been compared in nephrectomized dogs. These comparisons have been made under conditions which eliminate or minimize uncertainties regarding: a) extrarenal removal of these substances, b) changing plasma blank, c) completeness of recovery of the injected substance in the urine, and d) upper urinary tract dead space. The volumes of distribution of three of these substances, radiosulfate, thiosulfate, and mannitol, have been found to be equal. Sucrose, raffinose, and inulin volumes are smaller in inverse order to the molecular size of these substances.Volumes of distribution of d-galactose, d-xylose, and l-arabinose have been reported to increase in nephrectomized dogs and rabbits after insulin administration, presumably the result of insulin facilitating transport of these substances across cell membranes (8, 9). The possibility that endogenous insulin release might alter volumes of distribution of the six substances studied has been investigated by observing the effect of intravenous insulin on their volumes of distribution.
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