In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)

摘要: The hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. preclinical characterization of this highly promising comprised the evaluation its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, intestinal absorption using Caco-2 cell line. When mixed with active human liver microsomes, no loss parent compound was observed after 60 min, indicating stability presence microsomal P450. At tested concentrations, did not significantly influence activities any cytochromal isoforms screened. Thus, unlikely to cause drug-drug interactions by inhibiting metabolic clearance coadministered drugs metabolized these enzymes. Plasma protein-binding assays revealed that protein-bound dogs less extensively rats humans. In study, stable 1 h at 37°C mouse, rat, dog, samples. Finally, a bidirectional permeability assay demonstrated permeable across monolayer, highlighting need further evaluate effects various compounds known enhancement properties on future studies.