Renal transport of adefovir, cidofovir, and tenofovir by SLC22A family members (hOAT1, hOAT3, and hOCT2).

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Uwai Y, Ida H, Tsuji Y, Katsura T, Inui K

Renal transport of adefovir, cidofovir, and tenofovir by SLC22A family members (hOAT1, hOAT3, and hOCT2).

Pharm Res. 2007 Apr;24(4):811-5. Epub 2007 Feb 15.

PubMed ID

17372702 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Tenofovir disoproxil	Solute carrier family 22 member 6	Protein	Humans	Unknown	Substrate	Details
Tenofovir disoproxil	Solute carrier family 22 member 8	Protein	Humans	Unknown	Substrate	Details