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Direct In Vivo Huma...
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Dahlgren, DavidUppsala universitet,Institutionen för farmaci
(author)
Direct In Vivo Human Intestinal Permeability (P-eff) Determined with Different Clinical Perfusion and Intubation Methods
- Article/chapterEnglish2015
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Elsevier BV,2015
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LIBRIS-ID:oai:DiVA.org:uu-264083
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-264083URI
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https://doi.org/10.1002/jps.24258DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:for swepub-publicationtype
Notes
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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.
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Roos, CarlUppsala universitet,Institutionen för farmaci(Swepub:uu)carro115
(author)
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Sjögren, ErikUppsala universitet,Institutionen för farmaci(Swepub:uu)ersjo473
(author)
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Lennernäs, HansUppsala universitet,Institutionen för farmaci(Swepub:uu)hanslenn
(author)
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Uppsala universitetInstitutionen för farmaci
(creator_code:org_t)
Related titles
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In:Journal of Pharmaceutical Sciences: Elsevier BV104:9, s. 2702-27260022-35491520-6017
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