Relationship Between Drug Concentration in Plasma or Serum and Amount of Drug in the Body

Abstract

It is shown that the apparent volume of distribution at the steady state (Vd)ss in a two-compartmental open system cannot be used to relate the drug concentration in the plasma to the amount of drug in the body, except at the one point in time when the rate of change of the amount of drug in the peripheral compartment is zero. A new concept of apparent volume of distribution, recently introduced for the pharmacokinetic analysis of a three-compartmental open system, is now applied to the two-compartmental open system. This concept leads to the definition of the constant (Vd)β, which relates drug concentration in the plasma to the total amount of drug in the body at all times during the terminal exponential elimination phase (β phase), (Vd)β is shown to be identical to the apparent volume of distribution obtained from the area under the plasma curve equation for a two-compartmental open system. Since the area equation is independent of route of administration, (Vd)β can be obtained readily without having to resort to intra venous injection and very intensive blood sampling.