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.