American Journal of Biochemistry and Biotechnology

A Phenolic Ester of O-Desmethylvenlafaxine (ODV) Improves Uptake of ODV into the Brain

Yang Zhang, Zhichao Yang, Sen Zhao and Hongli Zhou

DOI : 10.3844/ajbbsp.2016.263.269

American Journal of Biochemistry and Biotechnology

Volume 12, Issue 4

Pages 263-269

Abstract

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.

Copyright

© 2016 Yang Zhang, Zhichao Yang, Sen Zhao and Hongli Zhou. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.