Kinetic models of induction: I. Persistence of the inducing substance

A kinetic model for induction is presented which includes the pharmacokinetics of the inducing agent. When simulations based on this model are carried out, they demonstrate situations where the observed rate constant governing the change from the basal to the induced state, or from the induced to the basal state, differs substantially from the true turnover rate constant. This arises from the confounding influences of the accumulation or persistence of either the inducing agent itself or some intermediary metabolic process. Depending on the relationships between the kinetic constants, there are four experimental subsets which require various interpretative schemes to obtain a correct estimate of the turnover rate constant. These interpretive schemes point out the necessity of measuring the pharmacokinetics of the inducer in all experiments.