HIV protease inhibitors: garlic supplements and first-pass intestinal metabolism impact on the therapeutic efficacy
Berginc, Katja (Author), Trdan Lušin, Tina (Author), Trontelj, Jurij (Author), Kristl, Albin (Author)

URLURL - Presentation file, Visit http://onlinelibrary.wiley.com/doi/10.1002/bdd.730/abstract This link opens in a new window

Background/Aims. The aim of this study was to elucidate the impact of first-pass intestinal metabolism to therapeutic efficacy of antiretrovirals and to ascertain interaction mechanisms between garlic supplements (aged garlic extract) and HIV-protease inhibitors. Methods. In vitro permeability through rat jejunum, Caco-2 cell monolayers was determined and CYP3A4 metabolism studies were performed. Results. Saquinavir and darunavir efflux from enterocytes into gastrointestinal lumen significantly increased in the presence of aged garlic extract, whereas their CYP3A4 metabolism was inhibited. In the case of saquinavir a significant increase of its efflux was observed also in the presence of lower ritonavir doses. Because both drugs bound to different binding sites on P-glycoprotein and/or multidrug resistance associated protein 2 than garlic phytochemicals or ritonavir, lower amounts of antiretrovirals were absorbed. Conclusions. The fractions of tested anti-HIV drugs absorbed could decrease significantly during self-medication with garlic supplements or ritonavir dose adjustments. Due to distinct saquinavir and darunavir preferences for binding sites on efflux transporters, the presence of other compounds (garlic phytochemicals, ritonavir), capable of influencing intestinal transporter-enzyme interplay, might lead to pharmacokinetic interactions observed in clinical studies and case reports with anti- HIV drugs.

Keywords:sakvinavir, česnov ekstrakt, darunavir, proteazni inhibitorji, AIDS, CYP3A4
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
Number of pages:str. 495-505
Numbering:Vol. 31, issue 8-9
ISSN on article:0142-2782
DOI:10.1002/bdd.730 Link is opened in a new window
COBISS.SI-ID:2893681 Link is opened in a new window
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Record is a part of a journal

Title:Biopharmaceutics & drug disposition
Shortened title:Biopharm. drug dispos.
COBISS.SI-ID:25099264 This link opens in a new window

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