APPLICATIONS AND SIMULATIONS OF A DISCONTINUOUS ORAL ABSORPTION PHARMACOKINETIC MODEL

Purpose. To illustrate the application of a discontinuous oral absorpt ion model to cimetidine and ranitidine plasma concentration versus tim e data to demonstrate the use of the model for drugs which display dis continuous oral absorption profiles, and to illustrate the effect of v arious model parameters on plasma drug concentration versus time profi les and bioavailability. Methods. A discontinuous oral absorption mode l was used to fit ranitidine and cimetidine serum concentrations follo wing oral and intravenous administration. The model was also used to s imulate bioavailability and plasma concentrations versus time profiles for various parameter values. Results. Serum concentrations following administration of ranitidine and cimetidine were well described by th e model, and parameter estimates obtained were in agreement with liter ature values. Simulations demonstrate the effects of various absorptio n parameters and gastrointestinal tract transit parameters on bioavail ability and plasma concentration profiles. Conclusions. This discontin uous oral absorption pharmacokinetic model can be a useful tool in cha racterizing absorption phases, disposition, and bioavailability of dru gs exhibiting two absorption peaks following oral administration.