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- Dahlgren, DavidUppsala universitet,Institutionen för farmaci (author)
Evaluation of drug permeability calculation based on luminal disappearance and plasma appearance in the rat single-pass intestinal perfusion model
- Article/chapterEnglish2019
Publisher, publication year, extent ...
- Elsevier BV,2019
- printrdacarrier
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- LIBRIS-ID:oai:DiVA.org:uu-396541
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-396541URI
- https://doi.org/10.1016/j.ejpb.2019.06.011DOI
Supplementary language notes
- Language:English
- Summary in:English
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Notes
- The rat single-pass intestinal perfusion (SPIP) model is commonly used to investigate gastrointestinal physiology and membrane drug transport. The SPIP model can be used with the intestinal segment inside or outside the abdomen. The rats can also be treated with parecoxib, a selective cycloxygenase-2 inhibitor that has been shown to affect some intestinal functions following abdominal surgery, such as motility, epithelial permeability, fluid flux and ion transport. However, the impact of extra-abdominal placement of the intestinal segment in combination with parecoxib on intestinal drug transport has not been investigated. There is also uncertainty how well intestinal permeability determinations based on luminal drug disappearance and plasma appearance correlate in the rat SPIP model. The main objective of this rat in vivo study was to investigate the effect of intra- vs. extra abdominal SPIP, with and without, pretreatment with parecoxib. The effect was evaluated by determining the difference in blood-to-lumen Cr-51-EDTA clearance, lumen-to-blood permeability of a cassette-dose of four model compounds (atenolol, enalaprilat, ketoprofen, and metoprolol), and water flux. The second objective was to compare the jejunal permeability values of the model drugs when determined based on luminal disappearance or plasma appearance. The study showed that the placement of the perfused jejunal segment, or the treatment with parecoxib, had minimal effects on membrane permeability and water flux. It was also shown that intestinal permeability of low permeability compounds should be determined on the basis of data from plasma appearance rather than lumina] disappearance. If permeability is calculated on the basis of luminal disappearance, it should preferably include negative values to increase the accuracy in the determinations.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmaceutiska vetenskaper hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmaceutical Sciences hsv//eng
- Intestinal perfusion
- Intestinal permeability
- Intestinal physiology
- Intestinal fluid transport
Added entries (persons, corporate bodies, meetings, titles ...)
- Roos, CarlUppsala universitet,Institutionen för farmaci(Swepub:uu)carro115 (author)
- Peters, KarstenUppsala universitet,Institutionen för farmaci(Swepub:uu)karpe774 (author)
- Lundqvist, A.AstraZeneca R&D, Gothenburg, Sweden (author)
- Tannergren, C.AstraZeneca R&D, Gothenburg, Sweden (author)
- Sjögren, Erik,1977-Uppsala universitet,Institutionen för farmaci(Swepub:uu)ersjo473 (author)
- Sjöblom, Markus,1973-Uppsala universitet,Sjöblom/Nylander: Gastrointestinal fysiologi(Swepub:uu)msj20812 (author)
- Lennernäs, HansUppsala universitet,Institutionen för farmaci(Swepub:uu)hanslenn (author)
- Uppsala universitetInstitutionen för farmaci (creator_code:org_t)
Related titles
- In:European journal of pharmaceutics and biopharmaceutics: Elsevier BV142, s. 31-370939-64111873-3441
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