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Volume of Distribution:
Volume of Distribution:
The volume, in an organism, throughout which a drug appears to have been distributed; the volume into which a drug appears to have been dissolved after administration to an organism. Symbolized by Vd.
Suppose a drug has been completely absorbed from its site of application, has reached an equilibrium in its distribution among the several tissues of the body, and that no biotransformation or excretion of the drug has occurred. If one knew the mass (dose) of drug administered and the average concentration of the drug in the body, the apparent volume into which the drug had been dissolved could be determined from the relationship or definition: concentration = mass/volume. Since these idealized conditions are unobtainable in practice, the volume of distribution of a drug can only be approximated using experimental data.
With the assumption that the concentration of the drug in the plasma (or serum) reflects the average drug concentration in its whole volume of distribution, plasma concentration can be plotted against time after drug administration, and the resulting line can be extrapolated to yield a fictive concentration (C0) "predicted" to have existed at the instant the drug was administered - further assuming instantaneous and complete administration, absorption, and distribution of the drug. Obviously, C0, is the value expected to have occurred at a time when mechanisms of biotransformation and excretion had no significant effect on the amount of drug in the body. Needless to say, it is assumed for proper interpretation of C0, that the drug as measured in the plasma is identical to the agent that was administered, and that the drug underwent no chemical alteration in the course of administration, absorption, or distribution.
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 inferable. 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.
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