Table 1

Input parameters used for simulations according to both TM and SFM on intestinal clearance and bioavailability

Oral doseDosep.o. 1001-a 1001-a
i.v. doseDosei.v. 1001-a 1001-a
Compartment volumes (ml)
 ReservoirVR 2001-a 2001-a
 Intestinal tissueVint 31-b
  Enterocyte layerVen 0.31-c
  Serosa and other tissuesVs 2.71-d
 Intestinal blood volumeVint,b 1.621-b
  Enterocyte bloodVen,b 0.1621-c
  Serosal bloodVs,b 1.4581-d
Flow rate (ml/min)
 Intestinal bloodQI 81-a
  Mucosa blood to enterocyte layerQen 0.81-e
  Serosa and other tissue bloodQs 7.21-f
Clearances (ml/min)
 Drug transport clearanceCLd 0.5  or 500.5  or 50
 Metabolic intrinsic clearanceCLm 0.1  to 501-g 0.1  to 50
 Secretory intrinsic clearanceCLsec 0  to 501-g 0  to 50
Absorption rate constant (min−1)ka 0.01  to 101-g 0.01  to 10
Luminal degradation rate constant (min−1)kg 0.51-g 0.5
  • 1-a Assigned parameters.

  • 1-b Value estimated based on Harrison and Gibaldi (1977) where 10 ml was used for a 360-g rat (including cecum and stomach) and the average intestinal weight = 3 g (ref. Doherty and Pang, 2000).

  • 1-c Value associated with the designated flow to the enterocytes (0.1 × QI).

  • 1-d Value associated with the designated flow to the serosal and other tissue layer (0.9 × QI).

  • 1-e Qen = 0.1 × QI(assigned).

  • 1-f Qs = 0.9 × QI(assigned).

  • 1-g Parameters varied during simulations.