Metabolism of nicousamide in rat and human liver in vitro

This paper is aimed to study the metabolic kinetics of nicousamide in rat liver microsomes and cytosol and to identify the major metabolite and drug metabolizing enzymes involved in the metabolism of nicousamide in rat and human liver microsomes by selective inhibitors in vitro. The concentration of nicousamide was determined by HPLC-UV method. The metabolite of nicousamide in rat and human liver microsomes was isolated and identified by LC-MS/MS. The major metabolite of nicousamide in rat and human liver microsomes was identified to be 3-(3′-carboxy-4′-hydroxy-anilino-carbo-)-6-amino-7-hydroxy-8-methyl-coumarin (M₁). The metabolite of nicousamide in rat plasma, urine, bile and liver was consistent with M₁. The metabolism of nicousamide can be catalyzed by several reductases, including CYP450 reductases, cytochrome b₅ reductases and CYP2C6 in rat liver microsomes, as well as xanthine oxidase and DT-diaphorase in rat liver cytosol.