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regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat

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regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat

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dc.contributor.author	Dahlgren, David
dc.contributor.author	Cano Cebrián, María José
dc.contributor.author	Olander, Tobias
dc.contributor.author	Hedeland, Mikael
dc.contributor.author	Sjöblom, Markus
dc.date.accessioned	2023-11-16T13:59:28Z
dc.date.available	2023-11-16T13:59:28Z
dc.date.issued	2020
dc.identifier.uri	https://hdl.handle.net/10550/91218
dc.description.abstract	Sufficient colonic absorption is necessary for all systemically acting drugs in dosage forms that release the drug in the large intestine. Preclinically, colonic absorption is often investigated using the rat single-pass intestinal perfusion model. This model can determine intestinal permeability based on luminal drug disappearance, as well as the effect of permeation enhancers on drug permeability. However, it is uncertain how accurate the rat single-pass intestinal perfusion model predicts regional intestinal permeability and absorption in human. There is also a shortage of systematic in vivo investigations of the direct effect of permeation enhancers in the small and large intestine. In this rat single-pass intestinal perfusion study, the jejunal and colonic permeability of two low permeability drugs (atenolol and enalaprilat) and two high-permeability ones (ketoprofen and metoprolol) was determined based on plasma appearance. These values were compared to already available corresponding human data from a study conducted in our lab. The colonic effect of four permeation enhancers¿sodium dodecyl sulfate, chitosan, ethylenediaminetetraacetic acid (EDTA), and caprate¿on drug permeability and transport of chromium EDTA (an established clinical marker for intestinal barrier integrity) was determined. There was no difference in jejunal and colonic permeability determined from plasma appearance data of any of the four model drugs. This questions the validity of the rat single-pass intestinal perfusion model for predicting human regional intestinal permeability. It was also shown that the effect of permeation enhancers on drug permeability in the colon was similar to previously reported data from the rat jejunum, whereas the transport of chromium EDTA was significantly higher (p < 0.05) in the colon than in jejunum. Therefore, the use of permeation enhancers for increasing colonic drug permeability has greater risks than potential medical rewards, as indicated by the higher permeation of chromium EDTA compared to the drugs.
dc.language.iso	eng
dc.relation.ispartof	Pharmaceutics, 2020, vol. 12, num. 3, p. 1-14
dc.source	Dahlgren, David Cano Cebrián, Maria Jose Olander, Tobias Hedeland, Mikael Sjöblom, Markus 2020 Regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat Pharmaceutics 12 3 1 14. https://doi.org/10.3390/pharmaceutics12030242
dc.subject	absorció intestinal
dc.subject	farmacologia
dc.title	regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat
dc.type	journal article
dc.date.updated	2023-11-16T13:59:29Z
dc.identifier.doi	10.3390/pharmaceutics12030242
dc.identifier.idgrec	136837
dc.rights.accessRights	open access