Armodafinil

Identification

Summary

Armodafinil is a stimulant used to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea, narcolepsy, or shift work disorder.

Brand Names
Nuvigil
Generic Name
Armodafinil
DrugBank Accession Number
DB06413
Background

Armodafinil is the enantiopure of the wakefulness-promoting agent modafinil (Provigil), and is indicated to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA), narcolepsy, or shift work disorder (SWD). Research has shown that armodafinil significantly improves driving simulator performance in patients with SWD. Armodafinil consists of the (−)-R-enantiomer of the racemic modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc. (a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd.) and was approved by the U.S. Food and Drug Administration (FDA) in June 2007.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 273.35
Monoisotopic: 273.082349901
Chemical Formula
C15H15NO2S
Synonyms
  • (–)-2-[(R)-(diphenylmethyl)sulfinyl]acetamide
  • (−)-(R)-modafinil
  • (−)-modafinil
  • (R)-(−)-modafinil
  • (R)-modafinil
  • Armodafinil
  • Armodafinilo
  • Armodafinilum
External IDs
  • CEP 10953
  • CEP-10952
  • CEP-10953
  • CRL 40982
  • CRL-40982

Pharmacology

Indication

Investigated for use/treatment in sleep disorders, obstructive sleep apnea, schizophrenia and schizoaffective disorders, depression, and bipolar disorders.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Not Available

Mechanism of action

Nuvigil (armodafinil) is a single-isomer of modafini. The exact mechanism of action is unknown. Armodafinil belongs to a class of drugs known as eugeroics, which are stimulants that provide long-lasting mental arousal. Pharmacologically, armodafinil does not bind to or inhibit several receptors and enzymes potentially relevant for sleep/wake regulation. Armodafinil is not a direct- or indirect-acting dopamine receptor agonist. However, in vitro, both armodafinil and modafinil bind to the dopamine transporter and inhibit dopamine reuptake. [Medilexicon]

TargetActionsOrganism
ASodium-dependent dopamine transporter
antagonist
inhibitor
Humans
Absorption

Tmax is 2 hours when fasted and can be delayed approximately 2-4 hours by food, potentially affecting the onset of action.

Volume of distribution

Apparent volume of distribution: 42L.

Protein binding

Specific data unavailable. Similar to modafinil: approximately 60%, primarily to albumin.

Metabolism

In vitro and in vivo data show that armodafinil undergoes hydrolytic deamidation, S-oxidation, and aromatic ring hydroxylation, with subsequent glucuronide conjugation of the hydroxylated products. Amide hydrolysis is the single most prominent metabolic pathway, with sulfone formation by cytochrome P450 (CYP) 3A4/5 being next in importance. The other oxidative products are formed too slowly in vitro to enable identification of the enzyme(s) responsible. Only two metabolites reach appreciable concentrations in plasma (i.e., R-modafinil acid and modafinil sulfone). Data specific to armodafinil disposition are not available.

Route of elimination

Not Available

Half-life

Terminal half-life is approximately 15 hours.

Clearance

The oral clearance of armodafinil is approximately 33 mL/min.

Adverse Effects
Adverseeffects
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Toxicity

Not Available

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
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Armodafinil.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Armodafinil.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Armodafinil.
AcetaminophenThe metabolism of Acetaminophen can be increased when combined with Armodafinil.
AcetohexamideThe metabolism of Acetohexamide can be decreased when combined with Armodafinil.
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be decreased when combined with Armodafinil.
AcyclovirThe metabolism of Acyclovir can be increased when combined with Armodafinil.
AgomelatineThe metabolism of Agomelatine can be increased when combined with Armodafinil.
AlbendazoleThe metabolism of Albendazole can be decreased when combined with Armodafinil.
AlectinibThe metabolism of Alectinib can be increased when combined with Armodafinil.
Interactions
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Food Interactions
  • Avoid alcohol.
  • Exercise caution with grapefruit products. Armodafinil is partially metabolized by CYP3A4, and grapefruit is a CYP3A4 inhibitor.
  • Exercise caution with St. John's Wort. Armodafinil is partially metabolized by CYP3A4, and St. John's Wort is a CYP3A4 inducer.
  • Take with or without food. Taking armodafinil with food can delay the Tmax by 2-4 hours.

Products

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Product Images
International/Other Brands
Neoresotyl (Drugtech)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ArmodafinilTablet200 mg/1OralAurobindo Pharma Limited2016-08-032023-05-31US flag
NuvigilTablet50 mg/1OralRebel Distributors2009-06-01Not applicableUS flag63459 0205 30 nlmimage10 c841e47f
NuvigilTablet50 mg/1OralKAISER FOUNDATION HOSPITALS2011-01-282013-08-31US flag
NuvigilTablet250 mg/1OralKAISER FOUNDATION HOSPITALS2011-01-282013-07-31US flag63459 0225 30 nlmimage10 c441e20f
NuvigilTablet150 mg/1OralStat Rx USA2009-06-01Not applicableUS flag16590 034520210407 15418 1jwrjab
NuvigilTablet250 mg/1OralStat Rx USA2009-06-01Not applicableUS flag16590 039420210407 15418 1e34q1m
NuvigilTablet150 mg/1OralLake Erie Medical DBA Quality Care Products LLC2009-06-012018-12-31US flag
NuvigilTablet150 mg/1OralA S Medication Solutions2009-06-01Not applicableUS flag63459 0215 30 nlmimage10 d11c6893
NuvigilTablet100 mg/1OralCephalon, Inc.2009-06-012009-08-14US flag
NuvigilTablet50 mg/1OralCephalon, Inc.2009-05-26Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ArmodafinilTablet100 mg/1OralActavis Pharma, Inc.2012-08-282012-08-28US flag
ArmodafinilTablet200 mg/1OralActavis Pharma, Inc.2012-08-282012-08-28US flag
ArmodafinilTablet50 mg/1OralLupin Pharmaceuticals, Inc.2016-11-28Not applicableUS flag
ArmodafinilTablet150 mg/1OralLupin Pharmaceuticals, Inc.2016-11-28Not applicableUS flag
ArmodafinilTablet200 mg/1OralLupin Pharmaceuticals, Inc.2016-11-28Not applicableUS flag
ArmodafinilTablet250 mg/1OralLupin Pharmaceuticals, Inc.2016-11-28Not applicableUS flag
ArmodafinilTablet150 mg/1Oralbryant ranch prepack2016-11-29Not applicableUS flag
ArmodafinilTablet250 mg/1Oralbryant ranch prepack2016-11-29Not applicableUS flag
ArmodafinilTablet150 mg/1Oralbryant ranch prepack2016-11-28Not applicableUS flag
ArmodafinilTablet250 mg/1Oralbryant ranch prepack2016-11-28Not applicableUS flag

Categories

ATC Codes
N06BA13 — Armodafinil
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Benzyl alkyl sulfoxides / Sulfoxides / Primary carboxylic acid amides / Sulfinyl compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Aromatic homomonocyclic compound / Benzyl alkyl sulfoxide / Benzyl sulfoxide / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Diphenylmethane / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
2-[(diphenylmethyl)sulfinyl]acetamide (CHEBI:77590)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
V63XWA605I
CAS number
112111-43-0
InChI Key
YFGHCGITMMYXAQ-LJQANCHMSA-N
InChI
InChI=1S/C15H15NO2S/c16-14(17)11-19(18)15(12-7-3-1-4-8-12)13-9-5-2-6-10-13/h1-10,15H,11H2,(H2,16,17)/t19-/m1/s1
IUPAC Name
2-[(R)-diphenylmethanesulfinyl]acetamide
SMILES
NC(=O)C[S@@](=O)C(C1=CC=CC=C1)C1=CC=CC=C1

References

Synthesis Reference

http://www.google.com/patents/EP2649187A2?cl=en http://www.google.com/patents/US20100036164

General References
  1. Lankford DA: Armodafinil: a new treatment for excessive sleepiness. Expert Opin Investig Drugs. 2008 Apr;17(4):565-73. doi: 10.1517/13543784.17.4.565 . [Article]
  2. Drake C, Gumenyuk V, Roth T, Howard R: Effects of armodafinil on simulated driving and alertness in shift work disorder. Sleep. 2014 Dec 1;37(12):1987-94. doi: 10.5665/sleep.4256. [Article]
  3. Link [Link]
KEGG Drug
D03215
PubChem Compound
9690109
PubChem Substance
310264870
ChemSpider
7962943
BindingDB
50336892
RxNav
641465
ChEBI
77590
ChEMBL
CHEMBL1201192
ZINC
ZINC000003831139
Drugs.com
Drugs.com Drug Page
Wikipedia
Armodafinil
FDA label
Download (837 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentDementia With Lewy Body Disease1
4CompletedTreatmentFatigue / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentFibromyalgia, Primary1
4CompletedTreatmentMajor Depressive Disorder (MDD) / Obstructive Sleep Apnea (OSA) / Persistent Depressive Disorder (Dysthymia) / Sleep disorders and disturbances1
4CompletedTreatmentMenopause1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenia1
4CompletedTreatmentSomnolence2
4TerminatedTreatmentDelayed Emergence From Anesthesia / Obstructive Sleep Apnea (OSA)1
4TerminatedTreatmentHepatitis C Virus (HCV) Infection1
3CompletedPreventionObesity (Disorder) / Premature Recovery From Anesthesia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral100 mg/1
TabletOral200 mg/1
TabletOral200 mg
TabletOral50 mg
TabletOral150 mg
Tablet, coatedOral150 mg
TabletOral150 mg/1
TabletOral250 mg/1
TabletOral50 mg/1
TabletOral
TabletOral250 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US4927855No1990-05-222010-04-22US flag
US7297346Yes2007-11-202024-05-29US flag
US7132570Yes2006-11-072024-06-18US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.622 mg/mLALOGPS
logP1.75ALOGPS
logP1.53ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)8.84ChemAxon
pKa (Strongest Basic)-4.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area60.16 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity77.39 m3·mol-1ChemAxon
Polarizability28.2 Å3ChemAxon
Number of Rings2ChemAxon
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Monoamine transmembrane transporter activity
Specific Function
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A3
Uniprot ID
Q01959
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. Loland CJ, Mereu M, Okunola OM, Cao J, Prisinzano TE, Mazier S, Kopajtic T, Shi L, Katz JL, Tanda G, Newman AH: R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. Biol Psychiatry. 2012 Sep 1;72(5):405-13. doi: 10.1016/j.biopsych.2012.03.022. Epub 2012 Apr 25. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [Article]
  2. Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [Article]
  3. Darwish M, Kirby M, Robertson P Jr, Hellriegel ET: Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects. Clin Pharmacokinet. 2008;47(1):61-74. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [Article]
  2. Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [Article]
  3. Darwish M, Kirby M, Robertson P Jr, Hellriegel ET: Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects. Clin Pharmacokinet. 2008;47(1):61-74. [Article]
  4. Robertson P Jr, Hellriegel ET, Arora S, Nelson M: Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers. Clin Pharmacol Ther. 2002 Jan;71(1):46-56. [Article]
  5. FDA table of interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [Article]
  2. Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [Article]
  3. Robertson P Jr, Hellriegel ET, Arora S, Nelson M: Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers. Clin Pharmacol Ther. 2002 Jan;71(1):46-56. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [Article]
  2. Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [Article]
  2. Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Robertson P Jr, Hellriegel ET: Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37. [Article]
  2. Robertson P, DeCory HH, Madan A, Parkinson A: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. Drug Metab Dispos. 2000 Jun;28(6):664-71. [Article]

Drug created on March 19, 2008 16:32 / Updated on February 21, 2021 18:52