During an iv infusion the drug concentration approaches biexponentially. An iv loading dose can be given with the infusion to achieve faster approach to .
A loading dose calculated based on the volume of the central compartment (Cpss . Vc) will achieve the desired conc initially. Because of the drug distribution to the peripheral compartment, the drug concentration declines transiently (possibly to subtherapeutic concentration) and then increases gradually to the desired steady state concentration.
A loading dose calculated based on the volume of distribution during the elimination phase (Cpss . Vdβ ) will avoid the transient decline in the plasma drug concentration to subtherapeutic concentration due to drug distribution. However this loading dose will produce very high concentration initially which may be toxic for drugs with narrow .
The loading dose should be calculated based on an average value for the volume of distribution (between Vc and Vdβ ).
Another alternative is to give a loading dose based on the volume of the central compartment, then give additional smaller iv bolus doses to compensate for the transient decline in the drug concentration.
