Identification

Summary

Idebenone is an analogue of ubiquinone used for the treatment of visual impairment in adolescent and adult patients with Leber’s Hereditary Optic Neuropathy (LHON).

Brand Names
Raxone
Generic Name
Idebenone
DrugBank Accession Number
DB09081
Background

Idebenone is a synthetic analogue of ubiquinone (also known as Coenzyme Q10), a vital cell antioxidant and essential component of the Electron Transport Chain (ETC). It has been proposed that by interacting with the ETC, idebenone increases ATP production required for mitochondrial function, reduces free radicals, inhibits lipid peroxidation, and consequently protects the lipid membrane and mitochondria from oxidative damage 2. More specifically, idebenone is thought to transfer electrons directly to complex III of the mitochondrial ETC, thereby circumventing complex I and restoring cellular energy (ATP) generation 4.

Due to its ability to reduce oxidative damage and improve ATP production, idebenone was originally investigated for its potential use in Alzheimer's Disease and other cognitivie disorders 3. Lack of improvement in cognitive function halted its production for these conditions, however it continues to be investigated for use in other conditions associated with mitochondrial damage.

Idebenone is currently only indicated for use by the European Medicines Agency (EMA) for the treatment of visual impairment in adolescent and adult patients with Leber’s Hereditary Optic Neuropathy (LHON). LHON is a mitochondrially inherited degeneration of retinal ganglion cells, resulting in acute central vision loss. Due to its biochemical mode of action, it's thought that idebenone may re-activate viable-but-inactive retinal ganglion cells (RGCs) in LHON patients 4. It is not currently approved for use by either the Food and Drug Administration (USA) or Health Canada.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 338.444
Monoisotopic: 338.209324066
Chemical Formula
C19H30O5
Synonyms
  • 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methyl-1,4-benzoquinone
  • 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methyl-p-benzoquinone
  • 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methylcyclohexa-2,5-diene-1,4-dione
  • 2,3-dimethoxy-5-methyl-6-(10'-hydroxydecyl)-1,4-benzoquinone
  • 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone
  • 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-p-benzoquinone
  • idebenona
  • idébénone
  • Idebenone
External IDs
  • BRN 2001459
  • BRN-2001459
  • BRN2001459
  • CV 2619
  • CV-2619
  • CV2619

Pharmacology

Indication

Idebenone is indicated for use by the European Medicines Agency (EMA) for the treatment of visual impairment in adolescent and adult patients with Leber’s Hereditary Optic Neuropathy (LHON). It is not currently approved for use by either the Food and Drug Administration (USA) or Health Canada 4.

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Associated Conditions
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Pharmacodynamics

Not Available

Mechanism of action

Idebenone is a synthetic analogue of ubiquinone (also known as Coenzyme Q10), a vital cell antioxidant and essential component of the Electron Transport Chain (ETC). It has been proposed that by interacting with the ETC, idebenone increases ATP production required for mitochondrial function, reduces free radicals, inhibits lipid peroxidation, and consequently protects the lipid membrane and mitochondria from oxidative damage 2. More specifically, idebenone is thought to transfer electrons directly to complex III of the mitochondrial ETC, thereby circumventing complex I and restoring cellular energy (ATP) generation 4.

Absorption

After oral administration, idebenone is rapidly absorbed. On repeat dosing, maximum plasma concentrations of idebenone are reached on average within 1 hour (median 0.67 h range: 0.33-2.00 h). Food increases the bioavailability of idebenone by approximately 5-7-fold and i therefore should always be administered with food 4.

Volume of distribution

Experimental data have shown that idebenone passes the blood-brain barrier and is distributed at significant concentrations in cerebral tissue. Following oral administration pharmacologically relevant concentrations of idebenone are detectable in the aqueous humor of the eye 4.

Protein binding

Not Available

Metabolism

Metabolism occurs by means of oxidative shortening of the side chain and by reduction of the quinone ring and conjugation to glucuronides and sulphates. Idebenone shows a high first pass metabolism resulting in conjugates of idebenone (glucuronides and sulphates (IDE-C)) and the Phase I metabolites QS10, QS6, and QS4 as well as their corresponding Phase II metabolites (glucuronides and sulphates (QS10+QS10-C, QS6+QS6-C, QS4+QS4-C)). The main metabolites in plasma are IDE-C and QS4+QS4-C 4.

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Route of elimination

The main route of elimination is metabolism, with the majority of dose excreted via the kidneys as metabolites. After a single or repeated oral dose of 750 mg of idebenone, QS4+QS4-C were the most prominent idebenone-derived metabolites in urine, representing on average between 49.3% and 68.3% of the total administered dose. QS6+QS6 represented 6.45% to 9.46%, whereas QS10+QS10-C and IDE+IDE-C were close to 1% or below 4.

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

The most commonly reported adverse reactions to idebenone are mild to moderate diarrhoea (usually not requiring the discontinuation of the treatment), nasopharyngitis, cough and back pain Label.

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
AbacavirAbacavir may decrease the excretion rate of Idebenone which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Idebenone which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Idebenone which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Idebenone which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Idebenone which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Idebenone which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Idebenone which could result in a higher serum level.
AcrivastineIdebenone may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Idebenone which could result in a higher serum level.
Adefovir dipivoxilAdefovir dipivoxil may decrease the excretion rate of Idebenone which could result in a higher serum level.
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Food Interactions
  • Take with food.

Products

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International/Other Brands
Sovrima
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CatenaTablet150 mgOralSanthera Pharmaceuticals (Switzerland) Limited2008-10-152013-04-30Canada flag
RaxoneTablet, film coated150 mgOralSanthera Pharmaceuticals (Deutschland) Gmb H2016-09-08Not applicableEU flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BERMAXIN 90/10/5 MG FILM TABLET ,FILM TABLET, 28 ADETIdebenone (90 mg) + Donepezil hydrochloride (10 mg) + Memantine hydrochloride (5 mg)Tablet, film coatedOralCELTİS İLAÇ SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag
BERMAXIN 90/10/5 MG FILM TABLET ,FILM TABLET, 84 ADETIdebenone (90 mg) + Donepezil hydrochloride (10 mg) + Memantine hydrochloride (5 mg)Tablet, film coatedOralCELTİS İLAÇ SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag
EVERON 90/5 MG FILM KAPLI TABLET ,100 TABLETIdebenone (90 mg) + Memantine hydrochloride (5 mg)Tablet, coatedOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
EVERON 90/5 MG FILM KAPLI TABLET ,50 TABLETIdebenone (90 mg) + Memantine hydrochloride (5 mg)Tablet, coatedOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
SALPEZIL 90/10 MG FILM KAPLI TABLET ,TABLET, 28 ADETIdebenone (90 mg) + Donepezil hydrochloride (10 mg)Tablet, coatedCELTİS İLAÇ SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag
SALPEZIL 90/10 MG FILM KAPLI TABLET ,TABLET, 84 ADETIdebenone (90 mg) + Donepezil hydrochloride (10 mg)Tablet, coatedCELTİS İLAÇ SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag

Categories

ATC Codes
N06BX13 — Idebenone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as ubiquinones. These are coenzyme Q derivatives containing a 5, 6-dimethoxy-3-methyl(1,4-benzoquinone) moiety to which an isoprenyl group is attached at ring position 2(or 6).
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Quinone and hydroquinone lipids
Direct Parent
Ubiquinones
Alternative Parents
Fatty alcohols / P-benzoquinones / Vinylogous esters / Primary alcohols / Organic oxides / Hydrocarbon derivatives
Substituents
Alcohol / Aliphatic homomonocyclic compound / Carbonyl group / Cyclic ketone / Fatty acyl / Fatty alcohol / Hydrocarbon derivative / Ketone / Organic oxide / Organic oxygen compound
Molecular Framework
Aliphatic homomonocyclic compounds
External Descriptors
primary alcohol, benzoquinones (CHEBI:31687)
Affected organisms
Not Available

Chemical Identifiers

UNII
HB6PN45W4J
CAS number
58186-27-9
InChI Key
JGPMMRGNQUBGND-UHFFFAOYSA-N
InChI
InChI=1S/C19H30O5/c1-14-15(12-10-8-6-4-5-7-9-11-13-20)17(22)19(24-3)18(23-2)16(14)21/h20H,4-13H2,1-3H3
IUPAC Name
2-(10-hydroxydecyl)-5,6-dimethoxy-3-methylcyclohexa-2,5-diene-1,4-dione
SMILES
COC1=C(OC)C(=O)C(CCCCCCCCCCO)=C(C)C1=O

References

General References
  1. Bodmer M, Vankan P, Dreier M, Kutz KW, Drewe J: Pharmacokinetics and metabolism of idebenone in healthy male subjects. Eur J Clin Pharmacol. 2009 May;65(5):493-501. doi: 10.1007/s00228-008-0596-1. Epub 2009 Jan 6. [Article]
  2. Zs -Nagy I: Chemistry, toxicology, pharmacology and pharmacokinetics of idebenone: a review. Arch Gerontol Geriatr. 1990 Nov-Dec;11(3):177-86. [Article]
  3. Gillis JC, Benefield P, McTavish D: Idebenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in age-related cognitive disorders. Drugs Aging. 1994 Aug;5(2):133-52. [Article]
  4. EMA Product Label [Link]
  5. TITCK Product Information: Everon (idebenone/memantine hydrochloride) film-coated tablets [Link]
Human Metabolome Database
HMDB0253376
KEGG Drug
D01750
PubChem Compound
12881464
PubChem Substance
310265009
ChemSpider
3558
BindingDB
50505498
RxNav
51296
ChEBI
31687
ChEMBL
CHEMBL252556
ZINC
ZINC000001542890
Drugs.com
Drugs.com Drug Page
Wikipedia
Idebenone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentLeber Hereditary Optic Neuropathy (Optic, Atrophy, Hereditary, Leber)1
4RecruitingPreventionMigraine1
3CompletedTreatmentAmbulatory Care / Duchenne's Muscular Dystrophy (DMD)1
3CompletedTreatmentFriedreich's Ataxia5
3RecruitingTreatmentHeadache Disorders / Migraine1
3TerminatedTreatmentDuchenne's Muscular Dystrophy (DMD)2
3WithdrawnNot AvailableLeber Hereditary Optic Neuropathy (Optic, Atrophy, Hereditary, Leber)1
2CompletedTreatmentDuchenne's Muscular Dystrophy (DMD)2
2CompletedTreatmentFriedreich's Ataxia1
2CompletedTreatmentLeber Hereditary Optic Neuropathy (Optic, Atrophy, Hereditary, Leber)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral
TabletOral150 mg
Tablet, coated
Tablet, coatedOral
TabletOral30 mg
Tablet, film coatedOral
Tablet, coated45 MG
Tablet, film coatedOral150 MG
Tablet, coated
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0163 mg/mLALOGPS
logP3.98ALOGPS
logP3.57Chemaxon
logS-4.3ALOGPS
pKa (Strongest Acidic)16.84Chemaxon
pKa (Strongest Basic)-2Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area72.83 Å2Chemaxon
Rotatable Bond Count12Chemaxon
Refractivity96.52 m3·mol-1Chemaxon
Polarizability39.56 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0072-0944000000-a92c002a2a095f43babd
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0932000000-16596a60138e58f99403

Drug created at August 28, 2015 22:33 / Updated at September 05, 2022 12:50