Linear pharmacokinetic models and vanishing exponential terms: Implications in pharmacokinetics

Abstract

A series of models more closely related than classical models to known facts about drug absorption and disposition are presented. It is shown that mathematically such models require the same number of exponential terms in the equation describing the plasma concentration following intravenous administration as in that describing the plasma concentration following oral administration. However, it is also shown that one or two of the exponential terms of the intravenous, and sometimes the oral, equation often are relatively unimportant and appear to vanish on stripping or fitting of data. This phenomenon leads to ambiguity concerning which model to assign to one or more sets of data. The number of potential models in a given situation has now been greatly increased. It is also shown that if data obey these models then neither the Wagner-Nelson nor the Loo-Riegelman method provides estimates of absorption rate constants when the A t /V p , t data are analyzed by conventional methods.