onr:"swepub:oai:DiVA.org:uu-222384"
Search: onr:"swepub:oai:DiVA.org:uu-222384" > Cytochrome P450 Inh...
- 1 of 1
- Previous record
- Next record
- To hitlist
Cytochrome P450 Inhibitory Properties of Common Efflux Transporter Inhibitors
- Englund, Gunilla (author)
-
- Lundquist, Patrik (author)
- Uppsala universitet,Institutionen för farmaci
- Skogastierna, Cristine (author)
- show more...
- Johansson, Jenny (author)
- Hoogstraate, Janet (author)
- Afzelius, Lovisa (author)
- Andersson, Tommy B. (author)
- Projean, Denis (author)
- show less...
- (creator_code:org_t)
- 2014-01-06
- 2014
- English.
- In: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 42:3, s. 441-447
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Drug transporter inhibitors are important tools to elucidate the contribution of transporters to drug disposition both in vitro and in vivo. These inhibitors are often unselective and affect several transporters as well as drug metabolizing enzymes, which can make experimental results difficult to interpret with confidence. We therefore tested 14 commonly used P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug-resistance associated protein (MRP) inhibitors as inhibitors of cytochrome P450 (P450) enzyme activities using recombinant enzymes. A subset of P-gp and/or CYP3A inhibitors were selected (cyclosporin A, elacridar, ketoconazole, quinidine, reserpine, and tacrolimus) for a comparison of P450 inhibition in human microsomes and hepatocytes. Most P-gp inhibitors showed CYP3A4 inhibition, with potencies often in a similar range as their P-gp inhibition, as well as less potent CYP2C19 inhibition. Other P450 enzymes were not strongly inhibited except a few cases of CYP2D6 inhibition. MRP and BCRP inhibitors showed limited P450 inhibition. Some inhibitors showed less P450 inhibition in human hepatocytes than human liver microsomes, for example, elacridar, probably due to differences in binding, permeability limitations, or active, P-gp mediated efflux of the inhibitor from the hepatocytes. Quinidine was a potent P450 inhibitor in hepatocytes but only showed weak inhibition in microsomes. Quinidine shows an extensive cellular uptake, which may potentiate intracellular P450 inhibition. Elacridar, described as a potent and selective P-gp inhibitor, displayed modest P450 inhibition in this study and is thus a useful model inhibitor to define the role of P-gp in drug disposition without interference with other processes.
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
- Drug Metabolism And Disposition (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Englund, Gunilla
- Lundquist, Patri ...
- Skogastierna, Cr ...
- Johansson, Jenny
- Hoogstraate, Jan ...
- Afzelius, Lovisa
- show more...
- Andersson, Tommy ...
- Projean, Denis
- show less...
- Articles in the publication
- Drug Metabolism ...
- By the university
- Uppsala University
- Karolinska Institutet
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
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.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
