A physiologic model for simulating gastrointestinal flow and drug absorption in rats.
OBJECTIVE
The development of a physiologically based absorption model for orally administered drugs in rats is described.


METHODS
Unlike other models that use a multicompartmental approach, the GI tract is modeled as a continuous tube with spatially varying properties. The mass transport through the intestinal lumen is described via an intestinal transit function. The only substance-specific input parameters of the model are the intestinal permeability coefficient and the solubility in the intestinal fluid. With this physiologic and physicochemical information, the complete temporal and spatial absorption profile can be calculated.


RESULTS
A first performance test using portal concentration data published in the literature yielded an excellent agreement between measured and simulated temporal absorption profiles in the portal vein. Furthermore, the dose dependence of a compound with solubility-limited fraction dose absorbed in rats (chlorothiazide) could be adequately described by the model.


CONCLUSIONS
The continuous absorption model is well suited to simulate drug flow and absorption in the GI tract of rats.
Willmann
Stefan
S
Bayer AG, Bayer Technology Services, Biophysics, 51368 Leverkusen, Germany. Stefan.Willmann.SW@bayertechnology.com
Schmitt
Walter
W
Keldenich
Jörg
J
Dressman
Jennifer B
JB
D000818:Animals; D004008:Diclofenac / Q000378:metabolism / Q000494:pharmacology; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D008956:Models, Chemical; D010539:Permeability; D051381:Rats; D012995:Solubility
D004008:Diclofenac