Direct In Vivo Human Intestinal Permeability (P-eff) Determined with Different Clinical Perfusion and Intubation Methods

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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmakologi och toxikologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmacology and Toxicology hsv//eng
absorption
bioavailability
biopharmaceutics classification system
human intestinal permeability
intestinal perfusion
intestinal transporters
oral drug delivery
pharmacokinetics
physiologically based pharmacokinetic modeling

Roos, CarlUppsala universitet,Institutionen för farmaci(Swepub:uu)carro115 (författare)
Sjögren, ErikUppsala universitet,Institutionen för farmaci(Swepub:uu)ersjo473 (författare)
Lennernäs, HansUppsala universitet,Institutionen för farmaci(Swepub:uu)hanslenn (författare)
Uppsala universitetInstitutionen för farmaci (creator_code:org_t)

Ingår i:Journal of Pharmaceutical Sciences: Elsevier BV104:9, s. 2702-27260022-35491520-6017

Av författaren/redakt...: Dahlgren, David; Roos, Carl; Sjögren, Erik; Lennernäs, Hans

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