TABLE 2

Parameters used for simultaneous fit of systemic and intraluminal data of [3H]digoxin

Parameter
Model
TM
SFM
Oral dose (%)a 100 100
i.v. dose (%)a 100 100
Volume (ml)
    Reservoir, VRa 200 200
    Total intestinal tissue, Vtb 3 3
    Enterocyte layer, Venc —g fQ × Vt
    Serosa and other tissues, Vsc — (1 - fQ) × Vt
    Total intestine blood volume, Vbb 1.6 1.6
    Enterocyte blood, Venbc — fQ × Vb
    Serosal blood, Vsbc — (1 - fQ) × Vb
    Intestine luminal volume, Vlb 2 2
    Unstirred water layer volume, Vwd 1.1 1.1
    Membrane bilayer volume, Vmbd 0.00011 0.00011
Total intestinal blood flow rate, Q (ml/min)a 8 8
    Mucosa blood flow to enterocyte layer, Qenc — fQ × Q
    Serosa and other tissue blood flow, Qsc — (1 - fQ) × Q
Exchange rate constant from rbc to plasma, k′rp = frbc × krp (min-1)e 1.81 1.81
Exchange rate constant from plasma to rbc, kpr (min-1)e 0.468 0.468
Unbound fraction of digoxin in plasma, fpe 0.64 0.64
Unbound fraction of digoxin in tissue, ftf
0.781
0.781

  • ↵ a Experimental values for intestinal perfusion.

  • ↵ b From Doherty and Pang (2000).

  • ↵ c Only a fraction (fQ) of the total blood flow perfused the enterocyte layer of mucosa where the Cyp3a and Pgp reside, and the remaining intestinal blood flow (1 - fQ)Q perfused the serosa and other structures.

  • ↵ d Calculated according to the radius of small intestine, 0.18 cm (Chiou, 1994), thickness of unstirred water layer, 100 μm (Anderson et al., 1988), and lipid bilayer membrane, 10 nm, and small intestine of length 100 cm.

  • ↵ e From Liu et al. (2005).

  • ↵ f Measured by ultrafiltration.

  • ↵ g —, not applicable.