The formulation of the principle of superposition in the presence of non-compliance and its applications in multiple dose pharmacokinetics.

The principle of superposition is an important tool for studying multiple dose pharmacokinetics. In this paper, the principle of superposition in the presence of noncompliance is formulated generally as a recursive formula. With this powerful tool, we are able to provide a simple proof under general conditions for the fundamental result that steady state AUC is equal to the single-dose AUC for any concentration curve. In another application of the principle of superposition, we establish the relationship between the steady state average concentration and patient compliance index.