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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.
Pharm Res. 2017 12 29; 35(1):2.PR

Abstract

PURPOSE

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.

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 P para) 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.

Authors+Show Affiliations

Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, Alicante, Spain. Pharmacokinetics and Pharmaceutical Technology, University of Valencia, Valencia, Spain.Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, Alicante, Spain.Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.Pharmacokinetics and Pharmaceutical Technology, University of Valencia, Valencia, Spain.Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, Alicante, Spain.Pharmacokinetics and Pharmaceutical Technology, University of Valencia, Valencia, Spain.Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, Alicante, Spain. mbermejo@goumh.umh.es.in-ADME Research, 1732 First Avenue, No.102, New York, New York, 10128, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29288412

Citation

Lozoya-Agullo, Isabel, et al. "Closed-Loop Doluisio (Colon, Small Intestine) and Single-Pass Intestinal Perfusion (Colon, Jejunum) in Rat-Biophysical Model and Predictions Based On Caco-2." Pharmaceutical Research, vol. 35, no. 1, 2017, p. 2.
Lozoya-Agullo I, Gonzalez-Alvarez I, Zur M, et al. Closed-Loop Doluisio (Colon, Small Intestine) and Single-Pass Intestinal Perfusion (Colon, Jejunum) in Rat-Biophysical Model and Predictions Based on Caco-2. Pharm Res. 2017;35(1):2.
Lozoya-Agullo, I., Gonzalez-Alvarez, I., Zur, M., Fine-Shamir, N., Cohen, Y., Markovic, M., Garrigues, T. M., Dahan, A., Gonzalez-Alvarez, M., Merino-Sanjuán, M., Bermejo, M., & Avdeef, A. (2017). Closed-Loop Doluisio (Colon, Small Intestine) and Single-Pass Intestinal Perfusion (Colon, Jejunum) in Rat-Biophysical Model and Predictions Based on Caco-2. Pharmaceutical Research, 35(1), 2. https://doi.org/10.1007/s11095-017-2331-z
Lozoya-Agullo I, et al. Closed-Loop Doluisio (Colon, Small Intestine) and Single-Pass Intestinal Perfusion (Colon, Jejunum) in Rat-Biophysical Model and Predictions Based On Caco-2. Pharm Res. 2017 12 29;35(1):2. PubMed PMID: 29288412.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Closed-Loop Doluisio (Colon, Small Intestine) and Single-Pass Intestinal Perfusion (Colon, Jejunum) in Rat-Biophysical Model and Predictions Based on Caco-2. AU - Lozoya-Agullo,Isabel, AU - Gonzalez-Alvarez,Isabel, AU - Zur,Moran, AU - Fine-Shamir,Noa, AU - Cohen,Yael, AU - Markovic,Milica, AU - Garrigues,Teresa M, AU - Dahan,Arik, AU - Gonzalez-Alvarez,Marta, AU - Merino-Sanjuán,Matilde, AU - Bermejo,Marival, AU - Avdeef,Alex, Y1 - 2017/12/29/ PY - 2017/08/03/received PY - 2017/12/18/accepted PY - 2017/12/31/entrez PY - 2017/12/31/pubmed PY - 2018/3/13/medline KW - Caco-2 KW - aqueous boundary layer permeability KW - dynamic range window (DRW) KW - paracellular permeability KW - rat colon and small intestinal perfusion methods SP - 2 EP - 2 JF - Pharmaceutical research JO - Pharm Res VL - 35 IS - 1 N2 - PURPOSE: 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. 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 P para) 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. SN - 1573-904X UR - https://www.unboundmedicine.com/medline/citation/29288412/Closed_Loop_Doluisio__Colon_Small_Intestine__and_Single_Pass_Intestinal_Perfusion__Colon_Jejunum__in_Rat_Biophysical_Model_and_Predictions_Based_on_Caco_2_ L2 - https://doi.org/10.1007/s11095-017-2331-z DB - PRIME DP - Unbound Medicine ER -