Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 104, Issue 9, Pages 2702-2726Publisher
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.24258
Keywords
absorption; bioavailability; biopharmaceutics classification system; human intestinal permeability; intestinal perfusion; intestinal transporters; oral drug delivery; pharmacokinetics; physiologically based pharmacokinetic modeling
Funding
- Innovative Medicines Initiative Joint Undertaking - European Union's Seventh Framework Programme (FP7) [115369]
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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. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2702-2726, 2015
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