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The influence of aged garlic extract on the uptake of Saquinavir and Darunavir into HepG2 cells and rat liver slices
Berginc, Katja (Author), Trontelj, Jurij (Author), Kristl, Albin (Author)

URLURL - Presentation file, Visit http://www.jstage.jst.go.jp/search/dmpk?dif2=and&d2=au&dp2=kristl&dif5=and&d5=te&dp5=&pl=20&search=Search#resultpoint This link opens in a new window

Abstract
Bioavailability and therapeutic outcome of treatment with HIV-protease inhibitors depends on intestinal and hepatic transporter-enzyme interplay. Liver transport of HIV protease inhibitors (saquinavir, darunavir) was assessed in the presence of aged garlic extract, because the HIV-infected often consume garlic supplements together with prescribed therapy. The in vitro uptake of both drugs into HepG2 cells and precision cut rat liver slicessignificantly increased in the presence of Pgp and MRP-2 inhibitor ritonavir. The incubation medium containing aged garlic extract caused significant inhibition of saquinavir efflux from HepG2 cells and precision cutliver slices, while the activity of darunavir efflux transporters in both liver models significantly increased. Due to opposite in vitro interactions observed between aged garlic extract and HIV protease inhibitors, darunavir and saquinavir most probably bind to different binding sites on one or both efflux transporters. Based on this study, coadministration of investigated compounds with garlic supplements could result in significant in vivo modification of hepatic transport-enzyme interplay, possibly leading to further bioavailability change.

Language:English
Keywords:HepG2 celice, česnov ekstrakt, darunavir, sakvinavir
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
Year:2010
Number of pages:str. 307-313
Numbering:vol. 25, no. 3
UDC:542
ISSN on article:1347-4367
COBISS.SI-ID:2827633 Link is opened in a new window
Views:668
Downloads:255
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Record is a part of a journal

Title:Drug metabolism and pharmacokinetics
Shortened title:Drug metabol. pharmacokinet.
Publisher:Japanese Society for the Study of Xenobiotics
ISSN:1347-4367
COBISS.SI-ID:2827377 This link opens in a new window

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