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Closed-Loop Doluisio (Colon, Small Intestine) and Single-Pass Intestinal Perfusion (Colon, Jejunum) in Rat—Biophysical Model and Predictions Based on Caco-2
- Source :
- Pharmaceutical Research. 35
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- The effective rat intestinal permeability (P eff ) was deconvolved using a biophysical model based on parameterized paracellular, aqueous boundary layer, transcellular permeabilities, and the villus-fold surface area expansion factor. 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. 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 P para ) than the small intestine. 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.
- Subjects :
- Male
Colon
Databases, Pharmaceutical
Pharmaceutical Science
02 engineering and technology
Models, Biological
030226 pharmacology & pharmacy
Permeability
Jejunum
03 medical and health sciences
0302 clinical medicine
In vivo
Intestine, Small
medicine
Animals
Humans
Pharmacokinetics
Pharmacology (medical)
Intestinal Mucosa
Organic Chemicals
Rats, Wistar
Transcellular
Pharmacology
Intestinal permeability
Chemistry
Organic Chemistry
Permeation
021001 nanoscience & nanotechnology
medicine.disease
Small intestine
Perfusion
medicine.anatomical_structure
Intestinal Absorption
Pharmaceutical Preparations
Caco-2
Paracellular transport
Biophysics
Molecular Medicine
Caco-2 Cells
0210 nano-technology
Biotechnology
Subjects
Details
- ISSN :
- 1573904X and 07248741
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Pharmaceutical Research
- Accession number :
- edsair.doi.dedup.....cfb6e53aa5400f3eca3840d32d67fc82