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• W2013324802 endingPage "902" @default.
• W2013324802 startingPage "896" @default.
• W2013324802 abstract "ABSTRACT Efflux proteins have been shown to greatly affect the uptake of antiretroviral drugs by cells and to hamper their access to the human immunodeficiency virus type 1 replication site. This study evaluated the factors that may lead to drug-drug interactions between emtricitabine (FTC), tenofovir (TFV), and efavirenz (EFV), including the modulation of efflux transporter expression and function. Peripheral blood mononuclear cells from healthy volunteers were used to determine whether or not an interaction between antiretroviral drugs and target cells occurred in any combination of FTC, TFV, EFV, FTC-TFV, TFV-EFV, or FTC-TFV-EFV. Following 20 h of treatment, intracellular drug concentrations were measured by liquid chromatography-tandem mass spectrometry. Efflux transporter functionality and inhibitor drug properties were assessed by measuring fluorescent dye efflux. ABCB1 (P-glycoprotein), ABCC 1 to 6 (multidrug resistance-associated protein), and OAT (organic anion transporter) expression in response to the treatments was quantified by semiquantitative real-time PCR. Cells treated with a double combination (FTC-TFV or TFV-EFV) or the triple combination (FTC-TFV-EFV) produced higher FTC and TFV intracellular concentrations than cells treated with FTC or TFV alone. However, no change in the EFV intracellular concentration was observed. FTC tended to induce abcc5 mRNA expression and EFV tended to induce abcc1 and abcc6 mRNA expression, whereas TFV tended to reduce mdr1 , abcc1 , abcc5 , and abcc6 mRNA expression. Under these conditions, a decrease in the functionality of ABCC was observed, and this decrease was associated with the direct inhibitory actions of these drugs. This in vitro study reveals a benefit of the combination FTC-TFV-EFV in terms of the intracellular FTC and TFV concentrations and highlights the pharmacological mechanisms that lead to this effect." @default.
• W2013324802 created "2016-06-24" @default.
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• W2013324802 date "2009-03-01" @default.
• W2013324802 modified "2023-10-18" @default.
• W2013324802 title "Combination of Tenofovir and Emtricitabine plus Efavirenz: In Vitro Modulation of ABC Transporter and Intracellular Drug Accumulation" @default.
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• W2013324802 doi "https://doi.org/10.1128/aac.00733-08" @default.
• W2013324802 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2650525" @default.
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