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Direct In Vivo Human Intestinal Permeability (P-eff) Determined with Different Clinical Perfusion and Intubation Methods
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2015 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 104, no 9, 2702-2726 p.Article, review/survey (Refereed) Published
Abstract [en]

Regional in vivo human intestinal effective permeability (P-eff) is calculated by measuring the disappearance rate of substances during intestinal perfusion. P-eff is the most relevant parameter in the prediction of rate and extent of drug absorption from all parts of the intestine. Today, human intestinal perfusions are not performed on a routine basis in drug development. Therefore, it would be beneficial to increase the accuracy of the in vitro and in silico tools used to evaluate the intestinal P-eff of novel drugs. This review compiles historical P-eff data from 273 individual measurements of 80 substances from 61 studies performed in all parts of the human intestinal tract. These substances include: drugs, monosaccharaides, amino acids, dipeptides, vitamins, steroids, bile acids, ions, fatty acids, and water. The review also discusses the determination and prediction of P-eff using in vitro and in silico methods such as quantitative structure-activity relationship, Caco-2, Ussing chamber, animal intestinal perfusion, and physiologically based pharmacokinetic (PBPK) modeling. Finally, we briefly outline how to acquire accurate human intestinal P-eff data by deconvolution of plasma concentration-time profiles following regional intestinal bolus dosing.

Place, publisher, year, edition, pages
2015. Vol. 104, no 9, 2702-2726 p.
Keyword [en]
absorption, bioavailability, biopharmaceutics classification system, human intestinal permeability, intestinal perfusion, intestinal transporters, oral drug delivery, pharmacokinetics, physiologically based pharmacokinetic modeling
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-264083DOI: 10.1002/jps.24258ISI: 000359857200006PubMedID: 25410736OAI: oai:DiVA.org:uu-264083DiVA: diva2:859004
Funder
EU, FP7, Seventh Framework Programme, 115369
Available from: 2015-10-05 Created: 2015-10-05 Last updated: 2017-12-01Bibliographically approved

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Dahlgren, DavidRoos, CarlSjögren, ErikLennernäs, Hans

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