Real and apparent volumes of distribution

Abstract

The real volume of distributionof a drug has physiological meaning, as it is related to the volume of body wateraccessible to the drug (including intracellular and extracellular fluid). Totalbody water represents 50%?70% of the total body weight; two thirds of itcorrespond to intracellular fluid, whereas the remaining one third correspondsto extracellular fluid (around 75% interstitial fluid and 25% plasma).Since an adult presents about 600 mL of body water per kilogram of bodyweight (which varies between 500 and 700 mL/kg depending on sex and age), the upper bound for the real volume ofdistribution of a drug will be around 42 L for a person weighing70 kg. No drug might have, for such an individual, a realvolume of distribution significantly above that approximate value. Furthermore,only a drug that can access all body volumes (plasma volume plus interstitialand intracellular fluids) would achieve the upper bound of the real volume ofdistribution. Conversely (i.e., if a drug does not fully distribute to a giventissue or organ), the real volume of distribution will be below thecorrespondent upper limit. After achieving systemic bioavailability, drugmolecules will almost instantaneously disperse within the plasma pool. Accordingly,the lower bound of the real volume of distribution would be the plasma volume,corresponding to a drug that can neither extravasate nor penetrate blood cells.Note that, as happens with other reference body volumes, plasma volume is alsosubject to significant variation across sex, age, body surface area, or diseasestates. For instance, male adults between 60 and 65 kg show plasma volumesclose to 3000 mL (mean plasma volume between 46.1 and 51.5 mL/kg,depending on the age group). The mean plasma volume per kilogram of body weighttends to be smaller in female adults, while a considerable plasma volumeexpansion (volume excess) has been observed in patients with chronic heartfailure.