zoniporide and 5-nitroquinoline

Many promising drug candidates metabolized by aldehyde oxidase (AOX) fail during clinical trial owing to underestimation of their clearance. AOX is species-specific, which makes traditional allometric studies a poor choice for estimating human clearance. Other studies have suggested using half-life calculated by measuring substrate depletion to measure clearance. In this study, we proposed using numerical fitting to enzymatic pathways other than Michaelis-Menten (MM) to avoid missing the initial high turnover rate of product formation. Here, product formation over a 240-minute time course of six AOX substrates-O

Topics: Acetamides; Acridines; Aldehyde Oxidase; Guanidines; Humans; Hydralazine; Kinetics; Liver; Nitroquinolines; Phthalazines; Pyrazoles; Pyrimidines; Reactive Oxygen Species