Sodium oxybate

Identification

Name
Sodium oxybate
Accession Number
DB09072
Description

Sodium oxybate (Xyrem) is a central nervous system depressant used for the treatment of cataplexy and extreme daytime sleepiness (EDS) associated with narcolepsy. It is the sodium salt of gamma hydroxybutyric acid (GHB) which is an endogenous compound and a metabolite of the neurotransmitter GABA. The exact mechanism of action for treating EDS and cataplexy is not known but is is hypothesised that its therapeutic effects are due to GABA(B) effects on noradrenergic, dopaminaergic and thalamocorticol neurons. The drug follows non-linear pharmacokinetics. As it has been associated with misuse/abuse it is strictly controlled and all patients and prescribers must enroll in the sodium oxybate REMs program in order to gain access to the medication.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 126.087
Monoisotopic: 126.02928837
Chemical Formula
C4H7NaO3
Synonyms
  • Oxybate sodium
  • Sodium oxybate
External IDs
  • NSC-84223
  • WY-3478

Pharmacology

Indication

For the treatment of cataplexy and excessive daytime sleepiness (EDS) associated with narcolepsy.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Sodium oxybate works through an unknown mechanism to treat narcolepsy by inducing sleep within about 5-15 minutes of administration.

Mechanism of action

The exact mechanism of action is unknown. It is the sodium salt of the endogenous compound gamma hydroxybutyrate which is a metabolite of the GABA neurotransmitter and it's thought that it's therapeutic effects are mediated via GABA B actions at noradrenergic, dopaminergic and thalamocortical neurons.

Absorption

Absolute bioavailability is approximately 88%. Tmax of 30.7-51.9min 2.

Volume of distribution

Vd of 37.7-67.7 2

Protein binding

Less then 1% is protein bound at concentrations ranging from 3 mcg/L to 300 mcg/L.

Metabolism

Animal studies indicate that the major elimination pathway is metabolism by the creation of carbon dioxide and water through the Krebs cycle and secondarily by beta-oxidation. In the primary pathway hydroxyacid-oxoacid transhydrogenase catalyzes the conversion of sodium oxybate to succinic semialdehyde which is then transformed to succinic acid by succinic semmialdehyde dehydrogenase. Succinic acid is then turned into carbon dioxide and water in the Krebs cycle. Succinic semialdehyde is also metabolised into carbon dioxide and water by a transhydrofenase in the presence of alpha ketoglutarate.

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Route of elimination

The major metabolite is carbon dioxide which is cleared by expiration, less then 5% appears as the unchanged drug in the urine within 6-8 hours after dosing.

Half-life

0.5 to 1 hour.

Clearance

Total clearance of 895-1361mL/min 2.

Adverse Effects
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Toxicity

Symptoms of overdose may include; depressed consciousness that may fluctuate rapidly between a confusional, agitated combative state with ataxia and coma, emesis, diaphoresis, headache and impaired psychomotor skills. Depth of coma varies with the amount ingested and myoclonus and tonic-clonic seizures have been reported. Oral LD50 of 9690mg/kg in rats MSDS.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcetazolamideSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Acetazolamide.
AcetophenazineSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Acetophenazine.
AclidiniumSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AgomelatineSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Agomelatine.
AlfentanilSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Alfentanil.
AlimemazineSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Alimemazine.
AlmotriptanSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Almotriptan.
AlosetronSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Alosetron.
AlprazolamAlprazolam may increase the central nervous system depressant (CNS depressant) activities of Sodium oxybate.
AlverineSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Alverine.
Additional Data Available
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  • Severity
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  • Evidence Level
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  • Action
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Food Interactions
  • Avoid alcohol.
  • Take separate from meals. Take sodium oxybate at least 2 hours after eating for optimal absorption.

Products

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Active Moieties
NameKindUNIICASInChI Key
gamma-Hydroxybutyric acidunknown30IW36W5B2591-81-1SJZRECIVHVDYJC-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
XyremSolution0.5 g/1mLOralJazz Pharmaceuticals, Inc.2002-07-17Not applicableUS flag
XyremSolution500 mgOralJazz Pharmaceuticals Ireland Limited2007-08-03Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
XywavSodium oxybate (0.5 g/1mL) + Calcium oxybate (0.5 g/1mL) + Potassium oxybate (0.5 g/1mL) + Magnesium oxybate (0.5 g/1mL)SolutionOralJazz Pharmaceuticals, Inc.2020-11-02Not applicableUS flag

Categories

ATC Codes
N01AX11 — Sodium oxybateN07XX04 — Sodium oxybate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as short-chain hydroxy acids and derivatives. These are hydroxy acids with an alkyl chain the contains less than 6 carbon atoms.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Hydroxy acids and derivatives
Sub Class
Short-chain hydroxy acids and derivatives
Direct Parent
Short-chain hydroxy acids and derivatives
Alternative Parents
Fatty acids and conjugates / Carboxylic acid salts / Monocarboxylic acids and derivatives / Carboxylic acids / Primary alcohols / Organic zwitterions / Organic sodium salts / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Alcohol / Aliphatic acyclic compound / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Carboxylic acid salt / Fatty acid / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Organic alkali metal salt
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
7G33012534
CAS number
502-85-2
InChI Key
XYGBKMMCQDZQOZ-UHFFFAOYSA-M
InChI
InChI=1S/C4H8O3.Na/c5-3-1-2-4(6)7;/h5H,1-3H2,(H,6,7);/q;+1/p-1
IUPAC Name
sodium 4-hydroxybutanoate
SMILES
[Na+].OCCCC([O-])=O

References

General References
  1. Lemon MD, Strain JD, Farver DK: Sodium oxybate for cataplexy. Ann Pharmacother. 2006 Mar;40(3):433-40; quiz 581-2. Epub 2006 Feb 28. [PubMed:16507620]
  2. Brenneisen R, Elsohly MA, Murphy TP, Passarelli J, Russmann S, Salamone SJ, Watson DE: Pharmacokinetics and excretion of gamma-hydroxybutyrate (GHB) in healthy subjects. J Anal Toxicol. 2004 Nov-Dec;28(8):625-30. [PubMed:15538955]
PubChem Compound
23663870
PubChem Substance
347827822
ChemSpider
9983
RxNav
9899
ChEMBL
CHEMBL1200682
Wikipedia
Sodium_oxybate
AHFS Codes
  • 28:92.00 — Miscellaneous Central Nervous System Agents
FDA label
Download (428 KB)
MSDS
Download (179 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceNarcolepsy With Cataplexy1
4CompletedBasic ScienceSleep1
4CompletedOtherMyalgic Encephalomyelitis (ME)1
4CompletedTreatmentAlcohol Dependence / Alcohol Withdrawal Syndrome1
4CompletedTreatmentNarcolepsy With Cataplexy1
4CompletedTreatmentObstructive Sleep Apnea (OSA)1
4RecruitingTreatmentREM Sleep Behavior Disorder1
4TerminatedTreatmentMild Alzheimer's Disease1
4TerminatedTreatmentMyalgic Encephalomyelitis (ME)1
4Unknown StatusTreatmentMyalgic Encephalomyelitis (ME)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
SolutionOral17.5 %
SolutionOral175 mg/ml
SyrupOral175 mg/ml
SolutionOral0.5 g/1mL
SolutionOral500 mg
SolutionOral500 mg/ml
SolutionOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7765106Yes2010-07-272024-12-16US flag
US6780889Yes2004-08-242021-01-04US flag
US7668730Yes2010-02-232024-12-16US flag
US7765107Yes2010-07-272024-12-16US flag
US7851506Yes2010-12-142020-06-22US flag
US7895059Yes2011-02-222023-06-17US flag
US8263650Yes2012-09-112020-06-22US flag
US8324275Yes2012-12-042020-06-22US flag
US8457988Yes2013-06-042023-06-17US flag
US8589182Yes2013-11-192023-06-17US flag
US8731963Yes2014-05-202023-06-17US flag
US8772306Yes2014-07-082033-09-15US flag
US8952062Yes2015-02-102020-06-22US flag
US9050302Yes2015-06-092033-09-15US flag
US7262219Yes2007-08-282021-01-04US flag
US8859619Yes2014-10-142020-06-22US flag
US9539330Yes2017-01-102020-06-22US flag
US9486426Yes2016-11-082033-09-15US flag
US10213400No2019-02-262033-03-15US flag
US10675258No2013-01-112033-01-11US flag
US8901173No2013-01-112033-01-11US flag
US10195168No2013-01-112033-01-11US flag
US8591922No2013-01-112033-01-11US flag
US9132107No2013-01-112033-01-11US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)145-146MSDS
Predicted Properties
PropertyValueSource
Water Solubility660.0 mg/mLALOGPS
logP-0.34ALOGPS
logP-0.51ChemAxon
logS0.72ALOGPS
pKa (Strongest Acidic)4.44ChemAxon
pKa (Strongest Basic)-2.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area60.36 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity34.64 m3·mol-1ChemAxon
Polarizability9.74 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Succinate-semialdehyde dehydrogenase [nad(p)+] activity
Specific Function
Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Gene Name
ALDH5A1
Uniprot ID
P51649
Uniprot Name
Succinate-semialdehyde dehydrogenase, mitochondrial
Molecular Weight
57214.23 Da
References
  1. Kim YG, Lee S, Kwon OS, Park SY, Lee SJ, Park BJ, Kim KJ: Redox-switch modulation of human SSADH by dynamic catalytic loop. EMBO J. 2009 Apr 8;28(7):959-68. doi: 10.1038/emboj.2009.40. Epub 2009 Mar 19. [PubMed:19300440]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Metal ion binding
Specific Function
Catalyzes the cofactor-independent reversible oxidation of gamma-hydroxybutyrate (GHB) to succinic semialdehyde (SSA) coupled to reduction of 2-ketoglutarate (2-KG) to D-2-hydroxyglutarate (D-2-HG)...
Gene Name
ADHFE1
Uniprot ID
Q8IWW8
Uniprot Name
Hydroxyacid-oxoacid transhydrogenase, mitochondrial
Molecular Weight
50307.42 Da
References
  1. Struys EA, Verhoeven NM, Ten Brink HJ, Wickenhagen WV, Gibson KM, Jakobs C: Kinetic characterization of human hydroxyacid-oxoacid transhydrogenase: relevance to D-2-hydroxyglutaric and gamma-hydroxybutyric acidurias. J Inherit Metab Dis. 2005;28(6):921-30. [PubMed:16435184]

Drug created on May 14, 2015 11:10 / Updated on November 25, 2020 15:47

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