Clearance = Dose / AUC

Clearance = Dose / AUC

The relationship between dose and concentration can be calculated independent of time. This now produces the most important formula of kinetics and is the basis of the linear relationship between dose and the Area Under the Curve (AUC). Remember that this only holds if the clearing organs remove a fixed percentage of the amount of drug offered to the organ, in other words, if the extraction ratio is constant.
Thus, if we start with the basic clearance equation:


(CA - CV) x Q / CA = Clearance


both sides can be multiplied by CA:

(CA - CV) x Q = Clearance x CA.


If the left side is added up to infinity it equals the dose, and the right side is equal to clearance times the AUC:
Dose = CL x AUC   or   Clearance = Dose / AUC.

 

Note that if the dose vs AUC is not a straight line, this is an indication for non-linear kinetics, often related to saturation of one of the ADME aspects. For example, if a small increase in dose leads to saturation of the metabolism, this immediately leads to a sharp increase in AUC. A clinical relevant example is phenytoin dosing.