Compartment- and model-independent linear plateau principle of drugs during a constant-rate absorption or intravenous infusion

Abstract

A simple general equation is derived to show the linear plateau principle under various conditions during or after a constant or changing rate of absorption or intravenous infusion. The time required to cause a certain fraction (f_t) of the total shift or change between the two steady-state plasma concentrations is equal to the time required for the cumulative (from time zero) plasma area, AUC_0→t, to reach the same fraction of AUC_0→∞ assumed to be obtained after an instantaneousintravenous dosing. The role of the terminal biological half-life and the importance of the earlydistribution phase and its exponential half-life or lives in the plateau principle are discussed.Clinical implications and applications to multiple dosage regimens are also discussed.