The Influence of Gender and Food on the Pharmacokinetics of Sodium Oxybate Oral Solution in Healthy Subjects

Borgen, Lowell A.; Okerholm, Richard A.; Morrison, Dennis; Lai, Allen A.

doi:10.1177/0091270002239707

Cited by 55 publications

(60 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…50 The ingestion of food with sodium oxybate has been shown to significantly reduce peak plasma concentrations and overall systemic absorption. 54 Ingestion of sodium oxybate after consuming a high-fat meal provided a maximum concentration of less than 50% of what is observed in a fasting state. 54 The time to reach maximum concentration was also significantly prolonged, and the AUC significantly decreased in the non-fasting group.…”

Section: Absorption and Distributionmentioning

confidence: 97%

“…50,54 It then undergoes extensive first-pass metabolism. 54,55 In fasted male and female volunteers 50 the mean maximum plasma concentration (C max ) after a single oral dose of sodium oxybate appeared to be dose dependent and was reached in mean time (t max ) of 25-75 minutes. 50,54,55 Administration of a second dose 4 hours later produced a 1.4-2.2 fold increase in mean C max .…”

Section: Absorption and Distributionmentioning

confidence: 99%

“…54,55 In fasted male and female volunteers 50 the mean maximum plasma concentration (C max ) after a single oral dose of sodium oxybate appeared to be dose dependent and was reached in mean time (t max ) of 25-75 minutes. 50,54,55 Administration of a second dose 4 hours later produced a 1.4-2.2 fold increase in mean C max . 53 The mean area under the plasma concentration curve from zero time to infinity (AUC) was nonlinearly dose dependent with a 2.5 to 2.8 fold increase in mean AUC in response to a 2-fold increase in dose, which may reflect capacity-limited absorption.…”

Section: Absorption and Distributionmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacotherapy of Narcolepsy: Focus on Sodium Oxybate

Kothare

Kaleyias

2010

Clinical Medicine Insights: Therapeutics

View full text Add to dashboard Cite

Narcolepsy is a complex disease with multiple symptoms that include excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. Pharmacologic management of patients with narcolepsy is based on treating these symptoms. Sodium oxybate, a neurotransmitter product of γ-amino butyric acid (GABA), is a Schedule III controlled substance in the US, approved for the treatment of excessive daytime sleepiness (EDS), and cataplexy in patients with narcolepsy.The purpose of this review is to summarize the current knowledge about treatment of narcolepsy with sodium oxybate and to familiarize readers with the safety and efficacy of sodium oxybate, thus enabling clinicians to optimize their management of narcolepsy. A review of the pharmacokinetics, pharmacodynamics, efficacy in different symptoms of narcolepsy, adverse effects, tolerability, and dosing of sodium oxybate is presented. Sodium oxybate administered as an oral solution has a rapid onset of effect, a short duration of action, and nearly complete metabolism with negligible unchanged γ-hydroxybutyrate (GHB) appearing in the urine. There is mounting evidence suggesting that GHB may function as an endogenous neuromodulator/neurotransmitter. The mechanism by which sodium oxybate has a therapeutic effect in narcolepsy is unclear. The efficacy of oral sodium oxybate on the treatment of narcolepsy was evaluated in two randomized, double-blind, placebo-controlled, multicenter, US and International trials. Treatment of patients with narcolepsy-cataplexy with sodium oxybate leads to reduction in the frequency of cataplexy attacks in a dose-related manner, improved EDS, increased level of alertness and ability to concentrate. The major problem with sodium oxybate remains in its potential for non-medical use to elicit altered states of consciousness; however, abuse and misuse of sodium oxybate has been rare over the 7 years since its introduction in the market. Other issues revolve around twice nightly dosing, and salty taste. The most commonly reported adverse events associated with the use of sodium oxybate and occurring with at least 5% greater frequency than seen in placebo-treated patients were dizziness, headache, nausea, pain, night terrors, enuresis, confusion, infection, vomiting, and urinary incontinence. In conclusion, sodium oxybate significantly improves all symptoms in patients with narcolepsy and is well tolerated.

show abstract

Section: Absorption and Distributionmentioning

confidence: 97%

Section: Absorption and Distributionmentioning

confidence: 99%

Section: Absorption and Distributionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacotherapy of Narcolepsy: Focus on Sodium Oxybate

Kothare

Kaleyias

2010

Clinical Medicine Insights: Therapeutics

View full text Add to dashboard Cite

show abstract

“…Dose administration after high-fat meals significantly reduces bioavailability of the drug (Borgen et al, 2003). GHB shows nonlinear pharmacokinetics.…”

Section: Neuropharmacology Of Ghbmentioning

confidence: 99%

Reconsidering GHB: orphan drug or new model antidepressant?

et al. 2011

View full text Add to dashboard Cite

For six decades, the principal mode of action of antidepressant drugs is the inhibition of monoamine re-uptake from the synaptic cleft. Tricyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs) and the new generation of dual antidepressants all exert their antidepressant effects by this mechanism. In the early days of the monoaminergic era, other efforts have been made to ameliorate the symptoms of depression by pharmacological means. The gamma-aminobutyric acid (GABA) system was and possibly still is one of the main alternative drug targets. Gammahydroxybutyrate (GHB) was developed as an orally active GABA analogue. It was tested in animal models of depression and human studies. The effects on sleep, agitation, anhedonia and depression were promising. However, the rise of benzodiazepines and tricyclic antidepressants brought GHB out of the scope of possible treatment alternatives. GHB is a GABA(B) and GHB receptor agonist with a unique spectrum of behavioural, neuroendocrine and sleep effects, and improves daytime sleepiness in various disorders such as narcolepsy, Parkinson's disease and fibromyalgia. Although it was banned from the US market at the end of the 1990s because of its abuse and overdose potential, it later was approved for the treatment of narcolepsy. New research methods and an extended view on other neurotransmitter systems as possible treatment targets of antidepressant treatment brought GHB back to the scene. This article discusses the unique neurobiological effects of GHB, its misuse potential and possible role as a model substance for the development of novel pharmacological treatment strategies in depressive disorders. AbstractFor six decades, the principal mode of action of antidepressant drugs is the inhibition of monoamine re-uptake from the synaptic cleft. Tricyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs) and the new generation of dual antidepressants all exert their antidepressant effects by this mechanism. In the early days of the monoaminergic era, other intents have been made to ameliorate symptoms of depression by pharmacological means.The gamma-aminobutyric acid (GABA) system was and possibly still is one of the main alternative drug targets. Gammahydroxybutyrate (GHB) was developed as an orally activeGABA analogue. It was tested in animal models of depression and human studies. The effects on sleep, agitation, anhedonia and depression were promising. But the rise of benzodiazepines and tricyclic antidepressants brought GHB out of scope of possible treatment alternatives. GHB is a GABA B and GHB receptor agonist with a unique spectrum of behavioral, neuroendocrine and sleep effects, and improves daytime sleepiness in various disorders such as narcolepsy, Parkinson's disease and fibromyalgia. Although it was banned from the US-market end of the 1990-ies because of its abuse and overdose potential, it later was approved for the treatment of narcolepsy. New research methods and an extended view on other neurotransmitter systems a...

show abstract

“…SXB is typically taken at bedtime, with half the dose taken at the beginning of the night and the second half 24 h later. The drug needs to be taken on a relatively empty stomach because administration with a high-fat meal will seriously impede its absorption [Borgen et al 2003]. …”

Section: Treatment Of Fibromyalgiamentioning

confidence: 99%

Sodium Oxybate: A Potential New Pharmacological Option for the Treatment of Fibromyalgia Syndrome

Swick¹

2011

Therapeutic Advances in Musculoskeletal

View full text Add to dashboard Cite

Fibromyalgia syndrome (FMS) is a common disorder, characterized by diffuse pain and tenderness, stiffness, fatigue, affective disorders and significant sleep pathology. A new set of diagnostic criteria have been developed which should make it easier for a busy clinician to diagnose the condition. US Food and Drug Administration (FDA) approved medications for the treatment of FMS have, for the most part, been geared to modulate the pain pathways to give the patient some degree of relief. A different kind of pharmacological agent, sodium oxybate (SXB), is described that is currently approved for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. SXB, an endogenous metabolite of the inhibitory neurotransmitter gamma-hydroxybutyrate, is thought to act independently as a neurotransmitter with a presumed ability to modulate numerous other central nervous system neurotransmitters. In addition SXB has been shown to robustly increase slow wave sleep and decrease sleep fragmentation. Several large clinical trials have demonstrated SXB's ability to statistically improve pain, fatigue and a wide array of quality of life measurements of patients with fibromyalgia. SXB is not FDA approved to treat fibromyalgia.

show abstract

The Influence of Gender and Food on the Pharmacokinetics of Sodium Oxybate Oral Solution in Healthy Subjects

Cited by 55 publications

References 13 publications

Pharmacotherapy of Narcolepsy: Focus on Sodium Oxybate

Pharmacotherapy of Narcolepsy: Focus on Sodium Oxybate

Reconsidering GHB: orphan drug or new model antidepressant?

Sodium Oxybate: A Potential New Pharmacological Option for the Treatment of Fibromyalgia Syndrome

Contact Info

Product

Resources

About