Sodium oxybate: neurobiology and clinical efficacy

Abstract

Sodium oxybate is the sodium salt of γ-hydroxybutyrate (GHB), an endogenous short-chain fatty acid that is speculated to function as a neurotransmitter in the mammalian CNS. Pharmacodynamic effects of exogenously-administered sodium oxybate may include modulating the release of neurotransmitters, including γ-aminobutyric acid, dopamine, endogenous opioids and serotonin, and stimulating release of growth hormone. It is rapidly absorbed, with approximately 25% bioavailability and a plasma half-life of 40–60 min, necessitating twice-nightly dosing. Sodium oxybate is indicated for the treatment of cataplexy and excessive daytime sleepiness in patients with narcolepsy, and has been shown to improve disrupted night-time sleep and increase Stage 3 and 4 (slow-wave restorative) sleep in this patient population. The most common adverse events reported in clinical trials in patients with narcolepsy include headache, nausea, dizziness, nasopharyngitis, somnolence, vomiting and urinary incontinence.

Keywords: :

• γ-hydroxybutyrate
• cataplexy
• excessive daytime sleepiness
• narcolepsy
• sleep
• sleep disorders
• sodium oxybate

Acknowledgements

We gratefully acknowledge the editorial and graphical assistance from Deborah Waxman, Teresa Steininger, PhD. and Star Wescott, all from Jazz Pharmaceuticals, and Carl S Hornfeldt, PhD, RPh, Apothekon, Inc., a consultant to Jazz Pharmaceuticals.