How Does the Distribution of a Drug Influence its Pharmacokinetics?
The volume of distribution (Vd) is an important indicator of the pharmacokinetic behaviour of a drug. First, it suggests the extent of the drug's distribution and its tissue binding. Second, it is the volume of fluid that must be cleared of the drug before elimination is complete and therefore influences how long it takes for the dose to be completely eliminated. Although elimination only takes place from the central compartment, it will not be complete until every last molecule has diffused back from the peripheral to the central compartment.
It should be noted that Vd is a constant for a specific drug and is independent of the dose or the plasma concentration of the drug. At any time during a drug's residence in the body, Vd relates the amount of drug remaining in the body to the drug concentration in plasma.
Moreover, because it influences the rate of drug elimination, Vd is one of the determinants of half-life (the time taken for the amount of drug in the body, or the plasma concentration, to fall by half). The other determinant is clearance, the rate at which drug is removed from the volume of distribution, which will be described in detail in the next session. Not only is half-life an important factor in the rate of elimination, it is also an important determinant of the time taken to reach steady state after repeated drug dosing.
The interrelationship of the initial concentration (C0), the elimination rate constant (k), clearance rate (Cl), volume of distribution (Vd), half-life (t 1/2) and the amount of drug in the body at any time (A) are described mathematically in Fig 14.
Fig 14 The relationship between key pharmacokinetic parameters. C0 = initial plasma concentration, k = elimination rate constant, Cl = clearance rate, Vd = volume of distribution, t 1/2 = half-life, A is the amount of drug in the body. The equations demonstrate how volume of distribution is directly related to half-life and inversely related to the rate of clearance.
