Identification

Name
Armodafinil
Accession Number
DB06413
Type
Small Molecule
Groups
Approved, Investigational
Description

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.

Structure
Thumb
Synonyms
  • (–)-2-[(R)-(diphenylmethyl)sulfinyl]acetamide
  • armodafinilo
  • R-modafinil
External IDs
CEP 10953 / CEP-10952 / CEP-10953 / CRL 40982 / CRL-40982 / UNII-V63XWA605I
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ArmodafinilTablet200 mg/1OralAurobindo Pharma Limited2016-08-03Not applicableUs
NuvigilTablet150 mg/1OralStat Rx USA2009-06-01Not applicableUs
NuvigilTablet50 mg/1OralRebel Distributors2009-06-01Not applicableUs63459 0205 30 nlmimage10 c841e47f
NuvigilTablet250 mg/1OralCephalon2009-05-26Not applicableUs
NuvigilTablet50 mg/1OralCephalon2009-05-26Not applicableUs
NuvigilTablet150 mg/1OralLake Erie Medical Dba Quality Care Produts Llc2009-06-01Not applicableUs
NuvigilTablet250 mg/1OralKaiser Foundations Hospitals2011-01-28Not applicableUs63459 0225 30 nlmimage10 c441e20f
NuvigilTablet200 mg/1OralCephalon2014-02-20Not applicableUs63459 0220 30 nlmimage10 d4386a53
NuvigilTablet250 mg/1OralLake Erie Medical Dba Quality Care Produts Llc2009-05-26Not applicableUs
NuvigilTablet250 mg/1OralStat Rx USA2009-06-01Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ArmodafinilTablet50 mg/1OralAurobindo Pharma2018-03-06Not applicableUs
ArmodafinilTablet150 mg/1OralBreckenridge Pharmaceutical, Inc.2016-11-28Not applicableUs
ArmodafinilTablet200 mg/1OralPreferred Pharmaceuticals Inc.2018-07-13Not applicableUs
ArmodafinilTablet250 mg/1OralSandoz2016-12-01Not applicableUs
ArmodafinilTablet100 mg/1OralWatson Pharmaceuticals2012-08-28Not applicableUs
ArmodafinilTablet150 mg/1OralTeva Pharmaceuticals USA, Inc.2016-11-29Not applicableUs
ArmodafinilTablet250 mg/1OralMylan Pharmaceuticals Inc.2016-06-01Not applicableUs
ArmodafinilTablet150 mg/1OralSandoz2016-12-01Not applicableUs
ArmodafinilTablet200 mg/1OralActavis Pharma Company2016-06-012021-05-31Us
ArmodafinilTablet200 mg/1OralLupin Pharmaceuticals2016-11-28Not applicableUs
International/Other Brands
Neoresotyl (Drugtech)
Categories
UNII
V63XWA605I
CAS number
112111-43-0
Weight
Average: 273.35
Monoisotopic: 273.082349901
Chemical Formula
C15H15NO2S
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

Pharmacology

Indication

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

Associated Conditions
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
Human
Absorption

Peak plasma concentrations are attained at approximately 2 hours when fasted, and can be delayed approximately 2-4 hours in a fed state. Since the delay in tmax is also associated with elevated plasma concentrations later in time, food can potentially affect the onset and time course of pharmacologic action for armodafinil.

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.

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Armodafinil.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Armodafinil.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Armodafinil.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Armodafinil.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Armodafinil.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Armodafinil.
8-azaguanineThe metabolism of 8-azaguanine can be increased when combined with Armodafinil.
8-chlorotheophyllineThe metabolism of 8-chlorotheophylline can be increased when combined with Armodafinil.
9-DeazaguanineThe metabolism of 9-Deazaguanine can be increased when combined with Armodafinil.
9-MethylguanineThe metabolism of 9-Methylguanine can be increased when combined with Armodafinil.
Food Interactions
Not Available

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 . [PubMed:18363520]
  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. [PubMed:25325498]
  3. Link [Link]
External Links
KEGG Drug
D03215
PubChem Compound
9690109
PubChem Substance
310264870
ChemSpider
7962943
BindingDB
50336892
ChEBI
77590
ChEMBL
CHEMBL1201192
Drugs.com
Drugs.com Drug Page
Wikipedia
Armodafinil
ATC Codes
N06BA13 — Armodafinil
FDA label
Download (837 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentNarcolepsy1
1, 2Active Not RecruitingTreatmentHead and Neck Carcinoma / Tiredness1
1, 2CompletedNot AvailableHealthy Volunteers1
1, 2TerminatedTreatmentHead and Neck Carcinoma1
1, 2WithdrawnSupportive CareLung Cancer Non-Small Cell Cancer (NSCLC)1
2Active Not RecruitingSupportive CareUnspecified Adult Solid Tumor, Protocol Specific1
2CompletedNot AvailableSleep Deprivation1
2CompletedSupportive CareCancer, Breast / Sleeplessness / Tiredness1
2CompletedSupportive CareCognition Disorders / Neoplasms, Brain / Nervous System Tumors / Tiredness1
2CompletedSupportive CareMalignant Gliomas1
2CompletedSupportive CareSleeplessness / Tiredness1
2CompletedTreatmentCerebrovascular Accidents / Hemiparesis / Strokes1
2CompletedTreatmentDepression, Bipolar1
2CompletedTreatmentEsophageal Cancers1
2CompletedTreatmentSchizophrenic Disorders2
2TerminatedSupportive CareMalignant Gliomas1
2TerminatedTreatmentChemotherapy Side Effects / Tiredness1
2, 3CompletedTreatmentDaytime Sleepiness / Nocturia1
2, 3CompletedTreatmentDisseminated Sclerosis1
2, 3CompletedTreatmentSarcoidosis / Sleepiness / Tiredness1
3CompletedPreventionBMI >30 kg/m2 / Obstructive Sleep Apnea (OSA) / Premature Recovery From Anesthesia1
3CompletedSupportive CareMultiple Myeloma (MM) / Tiredness1
3CompletedTreatmentBinge Eating Disorder (BED) / BMI >27 kg/m2 / Obese1
3CompletedTreatmentChronic Shift Work Sleep Disorder1
3CompletedTreatmentDepression3
3CompletedTreatmentExcessive Daytime Sleepiness / Narcolepsy / Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS)1
3CompletedTreatmentExcessive Sleepiness1
3CompletedTreatmentExcessive Sleepiness / Shift-work related sleep disturbance1
3CompletedTreatmentHypopnoea / Obstructive Sleep Apnea (OSA)1
3CompletedTreatmentNarcolepsy1
3CompletedTreatmentNarcolepsy / Shift-Work Sleep Disorder / Sleep Apnea Syndromes / Sleep Apnea, Obstructive1
3CompletedTreatmentObstructive Sleep Apnea (OSA) / Sleep Hypopnea1
3RecruitingSupportive CareTiredness1
3TerminatedTreatmentDepression1
3TerminatedTreatmentTraumatic Brain Injury (TBI)2
4CompletedTreatmentDelayed Emergence From Anesthesia / Obstructive Sleep Apnea (OSA)1
4CompletedTreatmentDiffuse Lewy Body Disease1
4CompletedTreatmentDysthymic Disorder / Major Depressive Disorder (MDD) / Obstructive Sleep Apnea (OSA) / Sleep disorders and disturbances1
4CompletedTreatmentExcessive Sleepiness2
4CompletedTreatmentFibromyalgia, Primary1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tiredness1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
4TerminatedTreatmentHepatitis C Viral Infection1
4Unknown StatusTreatmentMenopause1
Not AvailableActive Not RecruitingTreatmentSleep Apnea Syndrome / Sleeplessness1
Not AvailableCompletedSupportive CareLung Cancers1
Not AvailableRecruitingNot AvailableNarcolepsy / Obstructive Sleep Apnea (OSA) / Shift-work related sleep disturbance1
Not AvailableTerminatedTreatmentChronic Myeloid Leukemia (CML)1
Not AvailableUnknown StatusTreatmentLewy Bodies Disease / Parkinsons's Disease1
Not AvailableWithdrawnTreatmentLymphoma, B-Cell / Tiredness1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral100 mg/1
TabletOral200 mg/1
TabletOral150 mg/1
TabletOral250 mg/1
TabletOral50 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US4927855No1993-04-222010-04-22Us
US7297346Yes2004-05-292024-05-29Us
US7132570Yes2004-06-182024-06-18Us

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

Taxonomy

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
Diphenylmethane / Benzyl alkyl sulfoxide / Benzyl sulfoxide / Carboxamide group / Primary carboxylic acid amide / Sulfoxide / Sulfinyl compound / Carboxylic acid derivative / Hydrocarbon derivative / Carbonyl group
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
2-[(diphenylmethyl)sulfinyl]acetamide (CHEBI:77590)

Targets

Kind
Protein
Organism
Human
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. [PubMed:22537794]

Enzymes

Kind
Protein
Organism
Human
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. [PubMed:12537513]
  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. [PubMed:10820139]
  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. [PubMed:18076219]
Kind
Protein
Organism
Human
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. [PubMed:12537513]
  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. [PubMed:10820139]
  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. [PubMed:18076219]
  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. [PubMed:11823757]
Kind
Protein
Organism
Human
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. [PubMed:12537513]
  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. [PubMed:10820139]
  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. [PubMed:11823757]
Kind
Protein
Organism
Human
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. [PubMed:12537513]
  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. [PubMed:10820139]
Kind
Protein
Organism
Human
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. [PubMed:12537513]
  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. [PubMed:10820139]
Kind
Protein
Organism
Human
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. [PubMed:12537513]
  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. [PubMed:10820139]

Drug created on March 19, 2008 10:32 / Updated on November 02, 2018 06:16