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Direct In Vivo Huma...
Direct In Vivo Human Intestinal Permeability (P-eff) Determined with Different Clinical Perfusion and Intubation Methods
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- Dahlgren, David (författare)
- Uppsala universitet,Institutionen för farmaci
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- Roos, Carl (författare)
- Uppsala universitet,Institutionen för farmaci
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- Sjögren, Erik (författare)
- Uppsala universitet,Institutionen för farmaci
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- Lennernäs, Hans (författare)
- Uppsala universitet,Institutionen för farmaci
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- Engelska.
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 104:9, s. 2702-2726
- Relaterad länk:
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https://doi.org/10.1...
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http://jpharmsci.org...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- absorption
- bioavailability
- biopharmaceutics classification system
- human intestinal permeability
- intestinal perfusion
- intestinal transporters
- oral drug delivery
- pharmacokinetics
- physiologically based pharmacokinetic modeling
Publikations- och innehållstyp
- ref (ämneskategori)
- for (ämneskategori)
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