Mechanistic Study of the Distribution of Lascufloxacin into Epithelial Lining Fluid.

The present study aimed to clarify the mechanism underlying the high distribution of lascufloxacin in epithelial lining fluid (ELF). Involvement of transporters was examined by transcellular transport across Calu-3 and transporter-overexpressing cells; the binding of lascufloxacin to ELF components was examined by an organic solvent-water partitioning system that employed pulmonary surfactant and phospholipids. Transcellular transport across the transporter-overexpressing cells indicated lascufloxacin to be a substrate of both P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); therefore, its transport across Calu-3 cells was inhibited by P-gp and BCRP inhibitors.

Development and validation of bioanalytical methods for imidafenacin (KRP-197/ONO-8025) and its metabolites in human urine by using liquid chromatography-tandem mass spectrometry.

New bioanalytical methods have been developed for the determination of imidafenacin (KRP-197/ONO-8025, IM), a novel antimuscarinic drug developed for the treatment of overactive bladder, and its metabolites, M-2, M-3, M-4, M-6 and M-8 (method 1), M-5 and M-9 (method 2) in human urine by using liquid chromatography-tandem mass spectrometry. In each method, the urine sample was extracted by solid-phase extraction, separated on a semi-micro high-performance liquid chromatography column using gradient elution and detected by tandem mass spectrometer with an atmospheric pressure chemical ionization or ionspray interface. Extraction recoveries of IM and metabolites were 81.

Development and validation of bioanalytical methods for Imidafenacin (KRP-197/ONO-8025) and its metabolites in human plasma by liquid chromatography-tandem mass spectrometry.

Imidafenacin (KRP-197/ONO-8025, IM), 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide, is a new antimuscarinic agent currently under application for the indication of treatment of overactive bladder in Japan. We developed and validated the sensitive and selective bioanalytical methods for the extremely low levels of IM and its metabolite, M-2 (Method 1), M-4 (Method 2) and M-9 (Method 3) in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In each method, plasma sample was extracted by solid phase extraction, separated on a semi-micro high performance liquid chromatography column and detected by tandem mass spectrometer with an atmospheric pressure chemical ionization or ionspray interface.