TY  - JOUR
AU  - Zhang, Yang 
AU  - Yang, Zhichao 
AU  - Zhao, Sen 
AU  - Zhou, Hongli 
PY  - 2016
TI  - A Phenolic Ester of O-Desmethylvenlafaxine (ODV) Improves Uptake of ODV into the Brain
JF  - American Journal of Biochemistry and Biotechnology
VL  - 12
IS  - 4
DO  - 10.3844/ajbbsp.2016.263.269
UR  - https://thescipub.com/abstract/ajbbsp.2016.263.269
AB  - In this study, the in vitro stabilities of a promising O-Desmethylvenlafaxine (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 (t1/2) spans the range 5.0±0.18 d ~ 686±29.5 d. However, O-19 experiences rapid enzymatic hydrolysis in rat whole blood (t1/2 = 3.6±0.53 min) and rat liver microsomes (t1/2 = 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 (M1~M5) and faeces (M1, M4), no obvious toxic metabolite is detected.