A pharmacokinetic model for multiple sites discontinuous gastrointestinal absorption

Purpose. To build a pharmacokinetic model taking into account a discontinou s absorption along the gut, from n successive sites, a non-absorbing intest inal segment being always in between two successive sites. To solve the mat hematical model linked with the pharmacokinetic model to obtain the concent ration and contribution of each site to absorption, area under curve and bi oavailability. Methods. Whatever the number n of sites, we obtained the Laplace transform of amounts of drug in each site, then plasma concentration, so that concent ration or AUC were expressed analytically. When only two absorption sites a re present, concentration is obtained from Heaviside's theorem; but for n g reater than or equal to 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 sh ow the efficacy of each site. For n=3 sites, real data exhibiting three pea ks of various magnitude were fitted on our model. Conclusion. This general discontinuous oral absorption pharmacokinetic mode l may be taken as a possible tool to characterize each site of absorption a nd to estimate the area under curves or bioavailability. (C) 1999 IPEM. Pub lished by Elsevier Science Ltd. All rights reserved.