A novel prodrug strategy to improve the oral absorption of O-desmethylvenlafaxine

  • Authors:
    • Mingyuan Liu
    • Yantong Sun
    • Sen Zhao
    • Youxin Li
    • Riyang Piao
    • Yan Yang
    • Jingkai Gu
  • View Affiliations

  • Published online on: June 14, 2016     https://doi.org/10.3892/etm.2016.3453
  • Pages: 1611-1617
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Abstract

O-Desmethylvenlafaxine (desvenlafaxine, ODV) is the active metabolite of venlafaxine, with similar activity and less risk for pharmacokinetic drug interactions compared to its parent compound venlafaxine. The purpose of this study was to design a series of esters of ODV and assess their potential as ODV prodrugs with improved bioavailability and brain uptake. Seven esters were synthesized and pharmacokinetic screening was performed in rats. The monoester formed on the phenolic hydroxyl of ODV (ODVP‑1, ODVP‑2, ODVP‑3 and ODVP‑5) could be degraded to ODV in rat plasma. These four compounds confirmed as possible prodrugs were then studied to evaluated the relative bioavailability of ODV they produced in beagle dogs. ODVP‑1, ODVP‑2 and ODVP‑3 demonstrated higher relative bioavailability of ODV. Finally, ODVP‑1, ODVP‑2 and ODVP‑3 were studied to evaluate their brain uptake in rats. The concentration of ODV in the rat plasma, brain and hypothalamus after administration of ODVP‑1, ODVP‑2 or ODVP‑3 was higher compared with that of ODV. The higher bioavailability, improved pharmacokineics properties and more rapid penetration and translation of ODV suggest that ODVP‑1, ODVP‑2 or ODVP-3 may warrant further development and application as ODV prodrugs.
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September-2016
Volume 12 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Liu M, Sun Y, Zhao S, Li Y, Piao R, Yang Y and Gu J: A novel prodrug strategy to improve the oral absorption of O-desmethylvenlafaxine. Exp Ther Med 12: 1611-1617, 2016
APA
Liu, M., Sun, Y., Zhao, S., Li, Y., Piao, R., Yang, Y., & Gu, J. (2016). A novel prodrug strategy to improve the oral absorption of O-desmethylvenlafaxine. Experimental and Therapeutic Medicine, 12, 1611-1617. https://doi.org/10.3892/etm.2016.3453
MLA
Liu, M., Sun, Y., Zhao, S., Li, Y., Piao, R., Yang, Y., Gu, J."A novel prodrug strategy to improve the oral absorption of O-desmethylvenlafaxine". Experimental and Therapeutic Medicine 12.3 (2016): 1611-1617.
Chicago
Liu, M., Sun, Y., Zhao, S., Li, Y., Piao, R., Yang, Y., Gu, J."A novel prodrug strategy to improve the oral absorption of O-desmethylvenlafaxine". Experimental and Therapeutic Medicine 12, no. 3 (2016): 1611-1617. https://doi.org/10.3892/etm.2016.3453