Do we know that one of the most misunderstood pharmacokinetic (PK) parameters is volume of distribution (V)?
This is especially exacerbated by the many terminologies of V.
Let’s start with a simple yet important understanding that V is a proportionality factor that relates the amount of drug in the body to the concentration of drug measured in a biological fluid (e.g. plasma concentration or C). V is NOT a physiological volume.
But what about all of those different terms of V?
Using intravenous (IV) bolus, two-compartment scenario as an example, which V term [Vc (central compartment), V (distribution phase), Vss (steady-state) or Vβ (beta terminal phase)] should we use to calculate the loading dose (LD)?
Below are the different V terms and suggestions on how they can be used in PK analysis.
At time = zero hour, we can calculate Vc based on the IV bolus dose and the plasma concentration at time 0 h (C0). Vc is useful for predicting initial (peak) C after IV bolus dose.
At time = zero to t hours (distribution phase), V varies with time as drug is distributing from systemic circulation to the tissue compartment. It is not practical to measure V.
At time = t hour (steady-state). Considering no transporter activity and solely passive distribution, the unbound plasma concentration (Cu) equals unbound tissue concentration (CuT) at this inflection point. Vss calculated here is useful for estimating the LD. LD = Css × Vss where Css is desired or target plasma concentration at steady-state.
At time = t to infinity (∞) hours (beta terminal phase), Vβ is defined by β rate constant and comprises a net flow of drug from tissue to central compartment for elimination. Vβ is larger than Vss in this two-compartment scenario. If Vss is not available, a V value between Vc and Vβ may be used to estimate LD.
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Resource Person: Eric Chan, PhD