Effects of islatravir (4′-ethynyl-2-fluoro-2′-deoxyadenosine or EFdA) on renal tubular cells and islatravir's interactions with organic anion transporters

• Published in: Journal of pharmacological sciences Vol. 146; no. 2; pp. 82 - 87
• Main Authors: Kaneko, Meika, Reien, Yoshie, Morio, Hanae, Fukuuchi, Tomoko, Kaneko, Kiyoko, Hirayama, Yuri, Hashimoto, Hirofumi, Kuwata, Nobuyo, Mitsuya, Hiroaki, Anzai, Naohiko
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 01.06.2021; Elsevier
• Subjects: Islatravir; Kidney damage; Nucleoside reverse transcriptase inhibitors; Organic anion transporters; Renal tubular cells; Organic anion transporters; Islatravir; Kidney damage; Nucleoside reverse transcriptase inhibitors; Renal tubular cells
• ISSN: 1347-8613; 1347-8648; 1347-8648
• DOI: 10.1016/j.jphs.2021.03.004

Islatravir (ISL; 4′-ethynyl-2-fluoro-2′-deoxyadenosine or EFdA) is a novel reverse transcriptase translocation inhibitor and has a unique structure and high antiviral activity against wild-type and multidrug resistant HIV strains. In this study, we investigated whether islatravir (ISL) can cause kidney damage compared to tenofovir disoproxil fumarate (TDF) and tenofovir (TFV). We also investigated interactions of these drugs with organic anion transporters (OATs). There is a large gap in ISL concentration between the pharmacological dose to proximal tubular cells and the clinical dose. ISL is unlikely to be taken up via OAT1 or OAT3; therefore, OAT1 and OAT3 may not be involved in the injury to tubular cells. Present data strongly suggests that ISL is not toxic to proximal tubules because blood levels of ISL are not high enough to cause kidney damage in the clinical setting.