Citation:
תקציר:
Pharmacokinetic textbooks state that the (apparent) volume of distribution based on drug concentration in plasma (V or Vbeta) is always greater than the volume of distribution (apparent) under steady state conditions (Vss), but do not provide a general model-independent mathematical proof. Wagner's mathematical comparison between Vbeta and Vss is based on microscopic rate constants of either specific models and is restricted solely to the two-compartment open body model. Nakashima and Benet utilizing a model-dependent approach showed a mathematical relationship between Vbeta and Vss for a multicompartment model, but again by using microscopic model constants. The limitation of these two above mentioned mathematical comparisons is the necessity of knowledge of the model's structure and its microscopic rate constants. The present article describes a new non-compartmental, model-independent, general mathematical proof for Vbeta to be always greater than Vss. This new method does not require any knowledge of microscopical rate constants and is based solely on an exponentially decreasing function, which is the common way to describe drug disposition following i.v. bolus.