PURPOSE: The nephrotoxicity of the nucleotide antivirals adefovir, cidofovir and tenofovir is considered to depend on the renal tubular transport of them. Although it is known that the antivirals are substrates of the human renal organic anion transporter hOAT1 (SLC22A6), there is no information available on other organic ion transporters. The aim of the present study was to investigate whether the other renal organic anion transporter hOAT3 (SLC22A8) and organic cation transporter hOCT2 (SLC22A2) transport the antivirals. MATERIALS AND METHODS: Uptake experiments were performed using HEK293 cells transfected with cDNA of the organic ion transporters. RESULTS: The uptake of adefovir, cidofovir and tenofovir in monolayers stably expressing hOAT3 increased time-dependently, compared with control. Probenecid, a typical inhibitor of organic anion transporters, completely inhibited their transport. The amounts of the antivirals taken up by hOAT3 were much lower than those by hOAT1. The transient expression of hOCT2 did not increase uptake of the antivirals. CONCLUSION: These results indicate that adefovir, cidofovir and tenofovir are substrates of hOAT3 as well as hOAT1, but that quantitatively hOAT1 is the major renal transporter for these drugs.
PURPOSE: The nephrotoxicity of the nucleotide antivirals adefovir, cidofovir and tenofovir is considered to depend on the renal tubular transport of them. Although it is known that the antivirals are substrates of the human renal organic anion transporter hOAT1 (SLC22A6), there is no information available on other organic ion transporters. The aim of the present study was to investigate whether the other renal organic anion transporter hOAT3 (SLC22A8) and organic cation transporter hOCT2 (SLC22A2) transport the antivirals. MATERIALS AND METHODS: Uptake experiments were performed using HEK293 cells transfected with cDNA of the organic ion transporters. RESULTS: The uptake of adefovir, cidofovir and tenofovir in monolayers stably expressing hOAT3 increased time-dependently, compared with control. Probenecid, a typical inhibitor of organic anion transporters, completely inhibited their transport. The amounts of the antivirals taken up by hOAT3 were much lower than those by hOAT1. The transient expression of hOCT2 did not increase uptake of the antivirals. CONCLUSION: These results indicate that adefovir, cidofovir and tenofovir are substrates of hOAT3 as well as hOAT1, but that quantitatively hOAT1 is the major renal transporter for these drugs.
Authors: Megha A Nagle; David M Truong; Ankur V Dnyanmote; Sun-Young Ahn; Satish A Eraly; Wei Wu; Sanjay K Nigam Journal: J Biol Chem Date: 2010-10-04 Impact factor: 5.157
Authors: Jonghwa Lee; Mohammad Shahidullah; Adam Hotchkiss; Miguel Coca-Prados; Nicholas A Delamere; Ryan M Pelis Journal: Mol Pharmacol Date: 2015-02-06 Impact factor: 4.436
Authors: Amber Dahlin; Matthias Wittwer; Melanie de la Cruz; Jonathan M Woo; Rujuta Bam; Valeska Scharen-Guivel; John Flaherty; Adrian S Ray; Tomas Cihlar; Samir K Gupta; Kathleen M Giacomini Journal: Pharmacogenet Genomics Date: 2015-02 Impact factor: 2.089