SwePub
Sök i LIBRIS databas

  Extended search

L773:1742 206X OR L773:1742 2051
 

Search: L773:1742 206X OR L773:1742 2051 > Drug metabolome of ...

  • Aura, Anna-MarjaVTT Technical Research Centre of Finland, Espoo, Finland (author)

Drug metabolome of the simvastatin formed by human intestinal microbiota in vitro

  • Article/chapterEnglish2011

Publisher, publication year, extent ...

  • 2011
  • Royal Society of Chemistry,2011
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:oru-63638
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-63638URI
  • https://doi.org/10.1039/c0mb00023jDOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • The human colon contains a diverse microbial population which contributes to degradation and metabolism of food components. Drug metabolism in the colon is generally poorly understood. Metabolomics techniques and in vitro colon models are now available which afford detailed characterization of drug metabolites in the context of colon metabolism. The aim of this work was to identify novel drug metabolites of Simvastatin (SV) by using an anaerobic human in vitro colon model at body temperature coupled with systems biology platform, excluding the metabolism of the host liver and intestinal epithelia. Comprehensive two-dimensional gas chromatography with a time-of-flight mass spectrometry (GC×GC-TOFMS) was used for the metabolomic analysis. Metabolites showing the most significant differences in the active faecal suspension were elucidated in reference with SV fragmentation and compared with controls: inactive suspension or buffer with SV, or with active suspension alone. Finally, time courses of selected metabolites were investigated. Our data suggest that SV is degraded by hydrolytic cleavage of methylbutanoic acid from the SV backbone. Metabolism involves demethylation of dimethylbutanoic acid, hydroxylation/dehydroxylation and β-oxidation resulting in the production of 2-hydroxyisovaleric acid (3-methyl-2-hydroxybutanoic acid), 3-hydroxybutanoic acid and lactic acid (2-hydroxypropanoic acid), and finally re-cyclisation of heptanoic acid (possibly de-esterified and cleaved methylpyranyl arm) to produce cyclohexanecarboxylic acid. Our study elucidates a pathway of colonic microbial metabolism of SV as well as demonstrates the applicability of the in vitro colon model and metabolomics to the discovery of novel drug metabolites from drug response profiles.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Mattila, IsmoVTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Hyötyläinen, Tuulia,1971-Örebro universitet,Institutionen för naturvetenskap och teknik,VTT Technical Research Centre of Finland, Espoo, Finland(Swepub:oru)tihn (author)
  • Gopalacharyulu, PeddintiVTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Bounsaythip, CatherineUniversity of Helsinki, Helsinki, Finland (author)
  • Oresic, Matej,1967-Örebro universitet,Institutionen för medicinska vetenskaper,VTT Technical Research Centre of Finland, Espoo, Finland(Swepub:oru)moc (author)
  • Oksman-Caldentey, Kirsi-MarjaVTT Technical Research Centre of Finland, Espoo, Finland (author)
  • VTT Technical Research Centre of Finland, Espoo, FinlandInstitutionen för naturvetenskap och teknik (creator_code:org_t)

Related titles

  • In:Molecular Biosystems: Royal Society of Chemistry7:2, s. 437-4461742-206X1742-2051

Internet link

Find in a library

To the university's database

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view