Drug effects distribution

A. Historical Perspective Effect of the 1906 Act on Drug Product Distribution... 

The units of volume of distribution are those of volume (i.e. litres) and can be adjusted for, say, body weight. The two main uses of volume of distribution are in the calculation of loading doses for rapid onset of drug effect, and in understanding changes in half-life (see below). 

There may be several reasons for this pattern to be observed. One obvious reason is distribution, i.e. the drug needs time to reach its site of action, and the time lag between the measured drug concentration in plasma and the drug effect is due to distributional delay. In order to describe such a plasma concentration-effect relationship, a PK-PD model that allows for drug distribution to the site of action, e.g. the effect compartment model may be used. 

Drug distribution does not constitute the sole explanation for the appearance of a counter-clockwise hysteresis. Another reason may be that once the drug has reached its site of action, the cascade of receptor-related and post-receptor events leading to the measured drug effect takes time to develop and lags... 

Fig. 14. Schematic description of pharmacokinetic and pharmacodynamic determinants of drug action. Distribution from the measurement site (Cp) to the biophase (Ce), determined by a distribution rate constant is followed by drug-induced inhibition or stimulation of the production (k ) or removal (A out) of a mediator (R), transduction of the response R and further transformation of R to the measured effect E, if the measured effect variable is not R. (Modified from Jusko WJ, Ko HC, Ebling WF. Convergence of direct and indirect pharmacodynamic response models. J Pharmacokinet Biopharm 1995 23 5-6.)...

Changes in drug effects are often delayed in relation to changes in plasma concentration. This delay may reflect the time required for the drug to distribute from plasma to the site of action. This will be the case for almost all drugs. The delay due to... 

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