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.
Abbreviations
- hOAT:
-
human organic anion transporter
- hOCT:
-
human organic cation transporter
- MRP:
-
multidrug resistance protein.
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Acknowledgements
This work was supported in part by a grant-in-aid for Research on Advanced Medical Technology from the Ministry of Health, Labor and Welfare of Japan, by a Japan Health Science Foundation “Research on Health Sciences Focusing on Drug Innovation,” by a grant-in-aid for Scientific Research from the Ministry of Education, Science, Culture and Sports of Japan, and by the 21st Century COE program “Knowledge Information Infrastructure for Genome Science.”
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Uwai, Y., Ida, H., Tsuji, Y. et al. Renal Transport of Adefovir, Cidofovir, and Tenofovir by SLC22A Family Members (hOAT1, hOAT3, and hOCT2). Pharm Res 24, 811–815 (2007). https://doi.org/10.1007/s11095-006-9196-x
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DOI: https://doi.org/10.1007/s11095-006-9196-x