Applications and simulations of a discontinuous oral absorption pharmacokinetic model

Purpose. To illustrate the application of a discontinuous oral absorption model to cimetidine and ranitidine plasma concentration versus time data to demonstrate the use of the model for drugs which display discontinuous oral absorption profiles, and to illustrate the effect of various model parameters on plasma drug concentration versus time profiles and bioavailability. Methods. A discontinuous oral absorption model was used to fit ranitidine and cimetidine serum concentrations following oral and intravenous administration. The model was also used to simulate bioavailability and plasma concentrations versus time profiles for various parameter values. Results. Serum concentrations following administration of ranitidine and cimetidine were well described by the model, and parameter estimates obtained were in agreement with literature values. Simulations demonstrate the effects of various absorption parameters and gastrointestinal tract transit parameters on bioavailability and plasma concentration profiles. Conclusions. This discontinuous oral absorption pharmacokinetic model can be a useful tool in characterizing absorption phases, disposition, and bioavailability of drugs exhibiting two absorption peaks following oral administration.