Title page Involvement of Human Organic Cation Transporter 1 (OCT1) in the Hepatic Uptake of YM155 Monobromide, 1-(2-Methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)- 4,9-dihydro-1H-naphtho[2,3-d]imidazolium Bromide, a Novel, Small Molecule Survivi

Abstract

Abstract YM155 monobromide, 1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1H-naphtho[2,3-d]imidazolium bromide, which is a hydrophilic and cationic compound, exhibits anti-tumor activity in experimental human hormone refractory prostate carcinoma models. Urinary excretion was 18.3% to 28.6% of the dose in the clinical phase I study, and non-renal elimination may be explained by the biliary excretion of YM155 in its unchanged form. As the penetration through the sinusoidal membrane of the hepatocytes is the first step and an important part of biliary excretion, we evaluated the uptake o