THE VOLUME OF DISTRIBUTION OF MANNITOL AS A MEAS- URE OF THE VOLUME OF EXTRACELLULAR FLUID, WITH A STUDY OF THE MANNITOL METHOD'

The clearance of mannitol has been advocated by Smith and his coworkers as a measure of glomerular filtration rate (1). Newman, Bordley and Winternitz (2) modified Smith's procedure by calculating the clearance of mannitol from the rate of fall of concentration in serum after a single injection of the substance and suggested that the rate of glomerular filtration is more logically related to the volume of extracellular fluid than to body surface area. They also presented evi-dence that the volume of distribution of mannitol is of approximately the same magnitude as this fluid compartment. The thesis of Newman, Bordley and Winter-nitz that the clearance of mannitol can be calcu-lated from the fall in serum concentration alone is valid only if mannitol reaches a constant volume of distribution in the body. The determination of the volume of distribution rests on the fol-lowing assumptions: (1) that mannitol is neither formed nor destroyed in the body, (2) that it is distributed uniformly throughout some portion of the body water, (3) that its concentration in water of serum is a fair sample of its concentra-tion throughout this portion, and (4) that it is excreted solely in the urine (3). It is the pur-pose of this investigation to determine whether the apparent volume of distribution of mannitol meets the above basic assumptions, and to study the relation of this volume to that of extracellular fluid. Such a study requires a precise knowledge of the errors involved in the determination of man-nitol. For this reason the method of determina-tion and its accuracy were investigated in this laboratory and certain modifications introduced to minimize the error