Academic Journal
Molecular Assessment of the Potential for Renal Drug Interactions between Tenofovir and HIV Protease Inhibitors
| العنوان: | Molecular Assessment of the Potential for Renal Drug Interactions between Tenofovir and HIV Protease Inhibitors |
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| المؤلفون: | Cihlar, Tomas, Ray, Adrian S, Laflamme, Genevieve, Vela, Jennifer E, Tong, Leah, Fuller, Michael D, Roy, Anupma, Rhodes, Gerald R |
| المصدر: | Antiviral Therapy ; volume 12, issue 2, page 267-272 ; ISSN 1359-6535 2040-2058 |
| بيانات النشر: | SAGE Publications |
| سنة النشر: | 2007 |
| الوصف: | Background 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. Methods The effect of PIs on the transport of TFV by hOAT1, hOAT3 and MRP4 was assessed using in vitro cell-based transport models. Results At concentrations equal to their therapeutic peak plasma levels (C max ) all PIs showed <20% inhibition of TFV transport by hOAT1. hOAT3 was more sensitive to PIs with ritonavir (RTV) and lopinavir being the most potent inhibitors of TFV transport (62% and 37% inhibition, respectively, at their C max ). In the absence of human serum, RTV at concentrations exceeding its therapeutic C max also exhibited a minor effect on the cellular efflux of TFV by MRP4 (<30% inhibition at 20 μM). 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 C max . In addition, PIs did not affect the cytotoxicity of TFV or TDF in MRP4- or MRP2-overexpressing cells. Conclusion 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1177/135965350701200211 |
| الاتاحة: | https://doi.org/10.1177/135965350701200211 https://journals.sagepub.com/doi/pdf/10.1177/135965350701200211 |
| Rights: | https://journals.sagepub.com/page/policies/text-and-data-mining-license |
| رقم الانضمام: | edsbas.6CF2D702 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1177/135965350701200211 |
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