A pharmacokinetic model for multiple sites discontinuous gastrointestinal absorption

Purpose. To build a pharmacokinetic model taking into account a discontinous absorption along the gut, from n successive sites, a non-absorbing intestinal segment being always in between two successive sites. To solve the mathematical model linked with the pharmacokinetic model to obtain the concentration and contribution of each site to absorption, area under curve and bioavailability. Methods. Whatever the number n of sites, we obtained the Laplace transform of amounts of drug in each site, then plasma concentration, so that concentration or AUC were expressed analytically. When only two absorption sites are present, concentration is obtained from Heaviside's theorem; but for n≥3, Bromwich's theorem is necessary, a pole being of the order of more than two. Results. Simulations performed with data gathered from the literature allow to find, with n=2 sites, the particular case used for ranitinine and to show the efficacy of each site. For n=3 sites, real data exhibiting three peaks of various magnitude were fitted on our model. Conclusion. This general discontinuous oral absorption pharmacokinetic model may be taken as a possible tool to characterize each site of absorption and to estimate the area under curves or bioavailability.