RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
AstraZeneca Gothenburg, Cardiovasc & Metab Dis, Innovat Med & Early Dev, Gothenburg, Sweden..
AstraZeneca Gothenburg, Cardiovasc & Metab Dis, Innovat Med & Early Dev, Gothenburg, Sweden..
AstraZeneca Cambridge, Mass Spectrometry Imaging, Innovat Med & Early Dev, Drug Safety & Metab, Cambridge, England..
Vise andre og tillknytning
2017 (engelsk)Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 6352Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Knowledge about the region-specific absorption profiles from the gastrointestinal tract of orally administered drugs is a critical factor guiding dosage form selection in drug development. We have used a novel approach to study three well-characterized permeability and absorption marker drugs in the intestine. Propranolol and metoprolol (highly permeable compounds) and atenolol (low-moderate permeability compound) were orally co-administered to rats. The site of drug absorption was revealed by high spatial resolution matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and complemented by quantitative measurement of drug concentration in tissue homogenates. MALDI-MSI identified endogenous molecular markers that illustrated the villi structures and confirmed the different absorption sites assigned to histological landmarks for the three drugs. Propranolol and metoprolol showed a rapid absorption and shorter transit distance in contrast to atenolol, which was absorbed more slowly from more distal sites. This study provides novel insights into site specific absorption for each of the compounds along the crypt-villus axis, as well as confirming a proximal-distal absorption gradient along the intestine. The combined analytical approach allowed the quantification and spatial resolution of drug distribution in the intestine and provided experimental evidence for the suggested absorption behaviour of low and highly permeable compounds.

sted, utgiver, år, opplag, sider
NATURE PUBLISHING GROUP , 2017. Vol. 7, 6352
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-332846DOI: 10.1038/s41598-017-06583-4ISI: 000406273700004PubMedID: 28743866OAI: oai:DiVA.org:uu-332846DiVA: diva2:1155651
Forskningsfinansiär
Swedish Research Council, 2014-6215Swedish Foundation for Strategic Research , RIF14-0078Science for Life Laboratory - a national resource center for high-throughput molecular bioscience, 452300027AstraZeneca
Tilgjengelig fra: 2017-11-08 Laget: 2017-11-08 Sist oppdatert: 2017-11-08bibliografisk kontrollert

Open Access i DiVA

fulltext(4339 kB)4 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 4339 kBChecksum SHA-512
55198f9ef3cce4cad53f0558f71fc9a3512255633a484f137c55ceb754a7de53f242f8072f2353ae459f021fa03aee07d6a4af4cfcb0b9adb02d8c9f9a58bd84
Type fulltextMimetype application/pdf

Andre lenker

Forlagets fulltekstPubMed

Søk i DiVA

Av forfatter/redaktør
Nilsson, AnnaAndrén, Per E.
Av organisasjonen
I samme tidsskrift
Scientific Reports

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 4 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

Altmetric

Totalt: 135 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf