Direct In Vivo Human Intestinal Permeability (P-eff) Determined with Different Clinical Perfusion and Intubation Methods
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
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.
absorption, bioavailability, biopharmaceutics classification system, human intestinal permeability, intestinal perfusion, intestinal transporters, oral drug delivery, pharmacokinetics, physiologically based pharmacokinetic modeling
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:uu:diva-264083DOI: 10.1002/jps.24258ISI: 000359857200006PubMedID: 25410736OAI: oai:DiVA.org:uu-264083DiVA: diva2:859004
FunderEU, FP7, Seventh Framework Programme, 115369