title: Direct In Vivo Human Intestinal Permeability (Peff ) Determined with Different Clinical Perfusion and Intubation Methods.
abstract: Regional in vivo human intestinal effective permeability (Peff ) is calculated by measuring the disappearance rate of substances during intestinal perfusion. Peff 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 Peff of novel drugs. This review compiles historical Peff 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 Peff 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 Peff data by deconvolution of plasma concentration-time profiles following regional intestinal bolus dosing.
authors.affiliation: Department of Pharmacy, Uppsala University, Uppsala, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Dahlgren
authors.affiliation: Department of Pharmacy, Uppsala University, Uppsala, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Roos
authors.affiliation: Department of Pharmacy, Uppsala University, Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Sjögren
authors.affiliation: Department of Pharmacy, Uppsala University, Uppsala, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Lennernäs
mesh_terms: D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000502:physiology*; D007441:Intubation, Gastrointestinal; D010477:Perfusion; D010539:Permeability
keywords: absorption; bioavailability; biopharmaceutics classification system; human intestinal permeability; intestinal perfusion; intestinal transporters; oral drug delivery; pharmacokinetics; physiologically based pharmacokinetic modeling