Volume of Distribution (More...)

When C0 is divided into the mass of the total dose administered, the quotient indicated the volume into which the drug appears to be dissolved. When C0 is divided into dose expressed in terms of body weight (e.g.,mg/kg), the quotient is dimensionless - since kilograms and liters are considered equivalent - and indicates the fraction of body weight into which the drug appears to be dissolved. The volumes, or fractions, can be readily compared with parts of body weight occupied by the various fluid compartments (e.g., intravascular, extracellular, intracellular, etc.), and the approximate locus of drug distribution may be inferrable. A volume of distribution corresponding to more than about the volume of total body water is presumptive evidence that the drug is distributed nonuniformly throughout the body, and is concentrated at one or more sites, usually sites of drug storage, biotransformation or elimination, or at a site of drug application when a route of administration other than the intravenous one has been used. Obviously, legitimate and valid interpretation of calculated volume of distribution depends on the degree to which experimental facts are in concordance with the assumption given above. The idealized state is most closely approximated when the drug is given rapidly intravenously, and blood samples for chemical analysis of their drug content are taken at short intervals, beginning very soon after the time of drug administration.
Two more qualifications - first, special account must be taken mathematically, to yield validly interpretable volumes of distribution when binding of drug to plasma protein significantly restricts the mobility of drug molecules. Second, when the plot of plasma concentration against time gives evidence of a system involving two (or more) phases - i.e., two volumes into which drug tends to be distributed to different degrees at different times - special mathematical treatment of the data (more complicated than the treatment described above) is needed to permit calculation of the volumes of the several phases.
Cf. Compartment ,Pharmacokinetics, Half-Life, Vd (Vd).