REVIEW
Direct In Vivo Human Intestinal Permeability (Peff) Determined with Different Clinical Perfusion and Intubation Methods
David Dahlgren,
Carl Roos,
Erik Sjögren,
Hans Lennernäs,
David Dahlgren
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Search for more papers by this authorCarl Roos
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Search for more papers by this authorErik Sjögren
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Search for more papers by this authorCorresponding Author
Hans Lennernäs
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Telephone: +46-18471 4317; Fax: +46-18471-4223; E-mail: [email protected]Search for more papers by this authorDavid Dahlgren,
Carl Roos,
Erik Sjögren,
Hans Lennernäs,
David Dahlgren
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Search for more papers by this authorCarl Roos
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Search for more papers by this authorErik Sjögren
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Search for more papers by this authorCorresponding Author
Hans Lennernäs
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Telephone: +46-18471 4317; Fax: +46-18471-4223; E-mail: [email protected]Search for more papers by this authorAbstract
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. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2702–2726, 2015
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