Chemistry:Valiloxybate

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Valiloxybate (INN, USAN;[1] developmental code name XW-10172) is an extended-release prodrug of γ-hydroxybutyrate (GHB; oxybate) which is under development for the treatment of narcolepsy.[2][3][4][5][6] It is also being investigated for treatment of excessive daytime sleepiness (EDS) in people with Parkinson's disease.[7] The drug is taken orally once per night.[2][4][5][8][6]

Pharmacology

It is an amino acid (L-valine) ester prodrug of GHB,[6][1] which itself acts as a GABAB and GHB receptor agonist.[9][10] Relative to administration of GHB itself, valiloxybate showed a delayed time to peak levels and an extended duration of GHB exposure in humans.[6] It is said to maintain desired GHB levels for 6 to 7 hours.[11] This profile is compatible with once-nightly dosing,[6] in contrast to GHB itself which is typically administered twice per night due to its very short elimination half-life.[12][13][14] In addition, unlike sodium oxybate, valiloxybate contains no sodium or cation, and hence avoids excessive sodium intake.[6][15]

History

Valiloxybate is under development by XW labs or XWPharma.[2] As of September 2025, no recent development has been reported, but valiloxybate has reached phase 1 clinical trials for treatment of narcolepsy and phase 2 trials for treatment of sleeping problems in Parkinson's disease.[2][7]

See also

References

  1. ↑ 1.0 1.1 "VALILOXYBATE". https://drugs.ncats.io/substance/9B8NWP8K91. 
  2. ↑ 2.0 2.1 2.2 2.3 "Valiloxybate". 28 September 2025. https://adisinsight.springer.com/drugs/800051495. 
  3. ↑ "Valiloxibic acid". 28 July 2022. https://adisinsight.springer.com/drugs/800055229. 
  4. ↑ 4.0 4.1 "Therapeutic Use of γ-Hydroxybutyrate: History and Clinical Utility of Oxybates and Considerations of Once- and Twice-Nightly Dosing in Narcolepsy". CNS Drugs 39 (Suppl 1): 37–51. March 2025. doi:10.1007/s40263-024-01150-8. PMID 40111735. 
  5. ↑ 5.0 5.1 "Pharmacological options for narcolepsy: are they the way forward?". Expert Rev Neurother 23 (9): 819–834. 2023. doi:10.1080/14737175.2023.2249234. PMID 37585269. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 "501 Clinical PK of XW10172 for Once Nightly Therapy in Patients with Narcolepsy or Sleep Disorders in Neurodegenerative Diseases". Sleep 44 (Supplement_2): A197–A198. 3 May 2021. doi:10.1093/sleep/zsab072.500. ISSN 0161-8105. https://academic.oup.com/sleep/article-pdf/44/Supplement_2/A197/37655778/zsab072.500.pdf. Retrieved 30 September 2025. 
  7. ↑ 7.0 7.1 "Parkinson's disease therapy: what lies ahead?". J Neural Transm (Vienna) 130 (6): 793–820. June 2023. doi:10.1007/s00702-023-02641-6. PMID 37147404. 
  8. ↑ "Calcium, Magnesium, Potassium, and Sodium Oxybates Oral Solution: A Lower-Sodium Alternative for Cataplexy or Excessive Daytime Sleepiness Associated with Narcolepsy". Nat Sci Sleep 14: 531–546. 2022. doi:10.2147/NSS.S279345. PMID 35378745. 
  9. ↑ "DARK Classics in Chemical Neuroscience: Gamma-Hydroxybutyrate (GHB)". ACS Chem Neurosci 11 (23): 3850–3859. December 2020. doi:10.1021/acschemneuro.9b00336. PMID 31287661. 
  10. ↑ "International Union of Basic and Clinical Pharmacology. CXX. γ-Hydroxybutyrate protein targets in the mammalian brain-beyond classic receptors". Pharmacol Rev 77 (4). July 2025. doi:10.1016/j.pharmr.2025.100064. PMID 40449125. 
  11. ↑ "XWPharma Announces Positive Results from Phase 1 Clinical Trials of XW10172, in Development as Once-Nightly Therapy for Sleep Disorders in Patients with Neurodegenerative Diseases". GlobeNewswire News Room (Press release). 14 June 2021. Retrieved 30 September 2025.
  12. ↑ "Sodium oxybate: a review of its use in the management of narcolepsy". CNS Drugs 21 (4): 337–354. 2007. doi:10.2165/00023210-200721040-00007. PMID 17381187. 
  13. ↑ "Sodium oxybate for the treatment of fibromyalgia". Expert Opin Pharmacother 12 (11): 1789–1798. August 2011. doi:10.1517/14656566.2011.589836. PMID 21679091. 
  14. ↑ "Effects of oxybate dose and regimen on disrupted nighttime sleep and sleep architecture". Sleep Med 114: 255–265. February 2024. doi:10.1016/j.sleep.2023.12.015. PMID 38244463. 
  15. ↑ "Calcium, magnesium, potassium, and sodium oxybates oral solution for cataplexy or excessive daytime sleepiness associated with narcolepsy". Expert Opin Pharmacother 24 (8): 875–885. June 2023. doi:10.1080/14656566.2023.2204187. PMID 37060579. 


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