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• W1108614 endingPage "272" @default.
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• W1108614 abstract "Active renal secretion of tenofovir (TFV) across proximal tubules occurs via uptake by human organic anion transporters 1 and 3 (hOAT1 and hOAT3) coupled with efflux by multidrug resistance protein 4 (MRP4). Co-administration of some HIV protease inhibitors (PIs) with tenofovir disoproxil fumarate (TDF), an oral prodrug of TFV, has been shown to increase systemic levels of TFV, leading to a hypothesis that PIs may affect tubular secretion of TFV and potentially alter the renal safety of TDF.The effect of PIs on the transport of TFV by hOAT1, hOAT3 and MRP4 was assessed using in vitro cell-based transport models.At concentrations equal to their therapeutic peak plasma levels (Cmax) all PIs showed <20% inhibition of TFV transport by hOAT1. hOAT3 was more sensitive to Pls with ritonavir (RTV) and lopinavir being the most potent inhibitors of TFV transport (62% and 37% inhibition, respectively, at their Cmax). In the absence of human serum, RTV at concentrations exceeding its therapeutic Cmax also exhibited a minor effect on the cellular efflux of TFV by MRP4 (<30% inhibition at 20 microM). However, no effects of PIs on hOAT1, hOAT3 or MRP4 were detected in the presence of human serum with the exception of RTV that inhibited hOAT3 by approximately 35% at its Cmax. In addition, PIs did not affect the cytotoxicity of TFV or TDF in MRP4- or MRP2-overexpressing cells.These data indicate a low potential of PIs to interfere with the active tubular secretion of TFV and to alter the clinical renal safety profile of TDF." @default.
• W1108614 created "2016-06-24" @default.
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• W1108614 date "2007-02-01" @default.
• W1108614 modified "2023-10-18" @default.
• W1108614 title "Molecular Assessment of the Potential for Renal Drug Interactions between Tenofovir and HIV Protease Inhibitors" @default.
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• W1108614 doi "https://doi.org/10.1177/135965350701200211" @default.
• W1108614 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17503669" @default.
• W1108614 hasPublicationYear "2007" @default.
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