An In Silico Transwell Device for the Study of Drug Transport and Drug–Drug Interactions

Abstract

The ISTD is an example of a new class of simulation models capable of realistically representing complex drug transport and drug-drug interaction phenomena.

In Silico Methods for Unraveling the Mechanistic Complexities of Intestinal Absorption: Metabolism-Efflux Transport Interactions

“…1. It is a straightforward application of the already validated in silico transwell device (ISTD) (Garmire et al, 2007). It is an example of the synthetic modeling method .…”

“…For convenience, an abridged description of ISTD methods follows. For additional detail, consult (Garmire et al, 2007).…”

“…For S1, H is the radius of the simulated intestinal luminal content, 1.5 cm. As discussed by Garmire et al (2007), H for S1-4 corresponds to the typical height of the referent space in an epithelial cell monolayer. The values used are listed in Table 1.…”

“…Each element is also labeled with relevant chemical properties, such as pH (in silico pH); in this report, S1-4 pH ϭ 7.4. Tight junctions are as detailed by Garmire et al (2007). They occupy 0.066% of S1-4 elements.…”

“…The recently introduced synthetic modeling method (Grant et al, 2006;Hunt et al, 2006;Garmire et al, 2007;Tang et al, 2007;Yan et al, 2007) is intended specifically to engineer models that can be useful for gaining mechanistic insight into complex biological phenomena such as intestinal absorption of compounds that are substrates for both Pgp and CYP3A4. Such models can be constructed consistent with current knowledge using validated components.…”