Studies of intestinal drug transport using an in silico epithelio-mimetic device.
We report the development and use of a synthetic, discrete event, discrete space model that functions as an epithelio-mimetic device (EMD). It is intended to facilitate the study of intestinal transport of drug-like compounds. We represent passive paracellular and transcellular transport, carrier-mediated transport and active efflux using stand-alone components. Systematic verification of the EMD over a wide physiologically realistic range is essential before we can use it to address questions regarding the details of the interacting mechanisms that are believed to influence absorption. We report details of key verification experiments. We demonstrate that this device can generate behaviors similar to those observed in the in vitro Caco-2 transwell system. To do that we used a series of hypothetical drugs and we simulated behaviors for two clinically used drugs, alfentanil and digoxin. The results support the feasibility and practicability of the EMD as a tool to expand the experimental options for better understanding the biological processes involved in intestinal transport and absorption of compounds of interest.
Liu
Yu
Y
UCSF/UCB Joint Graduate Group in Bioengineering, University of California, Berkeley, CA, USA.
Hunt
C Anthony
CA
D015760:Alfentanil; D001692:Biological Transport / Q000502:physiology; D004077:Digoxin; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008954:Models, Biological; D010599:Pharmacokinetics; D049490:Systems Biology; D013997:Time Factors
D015760:Alfentanil; D004077:Digoxin