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

Pharm Res. 2007 Apr;24(4):811-5. doi: 10.1007/s11095-006-9196-x. Epub 2007 Feb 15.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / metabolism
  • Antiviral Agents / metabolism*
  • Cell Line
  • Cidofovir
  • Cytosine / analogs & derivatives
  • Cytosine / metabolism
  • Humans
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kinetics
  • Organic Anion Transport Protein 1 / metabolism
  • Organic Anion Transporters, Sodium-Independent / antagonists & inhibitors
  • Organic Anion Transporters, Sodium-Independent / genetics
  • Organic Anion Transporters, Sodium-Independent / metabolism*
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism*
  • Organic Cation Transporter 2
  • Organophosphonates / metabolism
  • Probenecid / pharmacology
  • Tenofovir
  • Transfection


  • Antiviral Agents
  • Organic Anion Transport Protein 1
  • Organic Anion Transporters, Sodium-Independent
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 2
  • Organophosphonates
  • SLC22A2 protein, human
  • organic anion transport protein 3
  • adefovir
  • Cytosine
  • Tenofovir
  • Adenine
  • Cidofovir
  • Probenecid