TABLE 1

ISID parameters

Category
Name
Description
Values
worldXSize Circumference of the inner intestine 75a,b
worldYSize Longitude length of the small intestine 4000a,c
tightJunctions Fraction of area occupied by pores 0.066%d
tjSize Pore radius 6.6 Åd
numCYP Number of cyps in S3 0–4800
numPGP Number of pgps in S2 0–4190
Cellular pH Simulated pH in S3 7.4
ISID S1 H The relative height of S1 1.5 × 106e,f
S2 H The relative height of S2 1c
S3 H The relative height of S3 2.0 × 103e,g
S4 H The relative height of S4 1e
conductorLength Length of a conductor, units 3a
biasFactor The parameter to control biased flow in S1 50a
molecularWeight MW 500
isAcid compound: a weak acid (otherwise, weak base) F
pKa compound's pKa 7.4
logPow Logarithm of partition coefficient 3
nonSpecficBinding Unitless factor of nonspecific binding in S3 0 to 1
Physicochemical properties of compounds ionDiffusion Permeation due to ionized form of drug 0 to 1
substrateOfCyp compound is a cyp substrate T or F
substrateOfPgp compound is a substrate of the pgps T or F
P1 (cyp) Probability of binding to cyps 0 to 1
P2 (cyp) Probability of releasing from cyps 0 to 1
P1 (pgp) Probability of binding to pgps 0 to 1
P2 (pgp) Probability of releasing from pgps 0 to 1
numSolutes compounds in conductor 1000
Experimental condition soluteVolume Conductor volume 3 ml
drugTypes Types of drugs in the simulation 1
s1pH, s5pH
Simulated S1 and S5 pH
7.4

  • ↵ a One ISID length-width unit maps to 0.125 cm

  • ↵ b Seventy-five width units map to the circumferences (3π cm) of human small intestines, calculated from the small intestinal diameter of 3.0 cm (Stubbs et al., 1998)

  • ↵ c Four thousand length units map to the 5-m length of a human small intestine (Lin et al., 1999)

  • ↵ d Values were optimized from Garmire et al. (2007)

  • ↵ e One unit of S1–4 element height maps to a typical membrane thickness of 7.5 to 10 nm (Garmire et al., 2007)

  • ↵ f According to Stubbs et al. (1998), 1.5 × 106 units of element height maps to a lumen radius of 1.5 cm

  • ↵ g According to Freitas (1999), 2.0 × 103 units of element height maps to the 20-μm thickness of epithelial cells