Garlic flavonoids and organosulfur compounds: the impact on saqunavir's and darunavir's hepatic pharmacokinetics

Berginc, Katja (author), Milisav, Irina (author), Kristl, Albin (author)

Saquinavir and darunavir therapeutic efficacy depends on the presence of xenobiotics (such as garlic compounds) capable of modifying transporter-enzymeinterplay. To ascertain the mechanism of interactions between antiretroviral drugs and garlic supplements and to identify responsible garlic constituents, hepatic pharmacokinetics of two antiretrovirals was investigated in the presence of garlic phytochemicals and aged garlic extract. For this purpose rat liver slices and isolated rat hepatocytes were used. Aged garlic extract significantly inhibited saquinavir efflux from the rat hepatocytes, while the efflux of darunavir significantly increased. Phytochemicals, inducing saquinavir and darunavir distribution changes were most probably flavonoids and lipophylic organosulfur compounds, respectively. All tested phytochemicals (except S-allyl L-cystein) and aged garlic extract also inhibited CYP3A4 metabolism of both drugs and modulated hepatic distribution of the corresponding saquinavir s and darunavir s metabolites. The competition between saquinavir and garlic constituent(s) for the same binding site on the efflux transporter and the positive-cooperative effect between darunavir and garlic phytochemical(s), which bind to separate binding places on transporter, are the most probable mechanisms to explain plasma profile changes, which could occur in vivo during concomitant consumption of antiretrovirals and garlic supplements.

• Language: English
• Keywords: česnov ekstrakt, darunavir, sakvinavir, podganja jetra
• Work type: Not categorized (r6)
• Tipology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Year: 2010
• Number of pages: str. 521-530
• Numbering: Vol. 25, no. 6
• UDC: 542:615
• ISSN on article: 1347-4367
• DOI: 10.2133/dmpk.DMPK-10-RG-053
• COBISS.SI-ID: 2929265
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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