A Phenolic Ester of <i>O</i>-Desmethylvenlafaxine (ODV) Improves Uptake of ODV into the Brain

Abstract

In this study, the in vitro stabilities of a promising ODesmethylvenlafaxine (ODV) phenolic ester prodrug O-19 in aqueous solution, rat whole blood and rat liver microsomes were investigated. In addition, the in vivo drug metabolites were determined using LC-TOFMS-IDA-MS/MS. O-19 exhibits high stabilities at any pH encountered in the gastrointestinal tract, its half live (t 1/2 ) spans the range 5.0±0.18 d ~ 686±29.5 d. However, O-19 experiences rapid enzymatic hydrolysis in rat whole blood (t 1/2 = 3.6±0.53 min) and rat liver microsomes (t 1/2 = 9.5±1.53 min). The metabolic profile of O-19 is similar to that of ODV. Besides ODV itself, five metabolites are identified in rat urine (M 1~M5 ) and faeces (M 1 , M 4 ), no obvious toxic metabolite is detected.

New natural antioxidants

“…Flavonoids (any of a large class of plant pigments having a structure based on or similar to that of flavone); such chemicals as carotenoids, flavonoids and phenols are generally present in foods of plant rather than animal origin (WILLIAMS, et al, 2004;ZHANG et al, 2016)…”