Brincidofovir Is Not a Substrate for the Human Organic Anion Transporter 1: A Mechanistic Explanation for the Lack of Nephrotoxicity Observed in Clinical Studies

摘要

Background:Brincidofovir (BCV) is an orally bioavailable lipid conjugate of cidofovir (CDV) with increased in vitro potency relative to CDV against all 5 families of double-stranded DNA viruses that cause human disease. After intravenous (IV) administration of CDV, the organic anion transporter 1 (OAT1) transports CDV from the blood into the renal proximal tubule epithelial cells with resulting dose-limiting nephrotoxicity.