Closed-Loop Doluisio (Colon, Small Intestine) and Single-Pass Intestinal Perfusion (Colon, Jejunum) in Rat—Biophysical Model and Predictions Based on Caco-2

Isabel Lozoya-Agullo, Isabel Gonzalez-Alvarez, Moran Zur, Noa Fine-Shamir, Yael Cohen, Milica Markovic, Teresa M. Garrigues, Arik Dahan, Marta Gonzalez-Alvarez, Matilde Merino-Sanjuán, Marival Bermejo, Alex Avdeef

Research output: Contribution to journalArticlepeer-review


Purpose: The effective rat intestinal permeability (Peff) was deconvolved using a biophysical model based on parameterized paracellular, aqueous boundary layer, transcellular permeabilities, and the villus-fold surface area expansion factor. Methods: Four types of rat intestinal perfusion data were considered: single-pass intestinal perfusion (SPIP) in the jejunum (n = 40), and colon (n = 15), closed-loop (Doluisio type) in the small intestine (n = 78), and colon (n = 74). Moreover, in vitro Caco-2 permeability values were used to predict rat in vivo values in the rat data studied. Results: Comparable number of molecules permeate via paracellular water channels as by the lipoidal transcellular route in the SPIP method, although in the closed-loop method, the paracellular route appears dominant in the colon. The aqueous boundary layer thickness in the small intestine is comparable to that found in unstirred in vitro monolayer assays; it is thinner in the colon. The mucosal surface area in anaesthetized rats is 0.96–1.4 times the smooth cylinder calculated value in the colon, and it is 3.1–3.6 times in the small intestine. The paracellular permeability of the intestine appeared to be greater in rat than human, with the colon showing more leakiness (higher Ppara) than the small intestine. Conclusion: Based on log intrinsic permeability values, the correlations between the in vitro and in vivo models ranged from r2 0.82 to 0.92. The SPIP-Doluisio method comparison indicated identical log permeability selectivity trend with negligible bias.

Original languageAmerican English
Article number2
JournalPharmaceutical Research
Issue number1
StatePublished - 1 Jan 2018


  • Caco-2
  • aqueous boundary layer permeability
  • dynamic range window (DRW)
  • paracellular permeability
  • rat colon and small intestinal perfusion methods

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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