Identification

Name
Nabumetone
Accession Number
DB00461  (APRD01128)
Type
Small Molecule
Groups
Approved
Description

Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID) of the arylalkanoic acid family (which includes diclofenac). Marketed under the brand name Relafen, it has been shown to have a slightly lower risk of gastrointestinal side effects than most other non-selective NSAIDs.

Structure
Thumb
Synonyms
  • 4-(6-Methoxy-2-naphthalenyl)-2-butanone
  • 4-(6-Methoxy-2-naphthyl)-2-butanone
  • Nabumeton
  • Nabumetona
  • Nabumétone
  • Nabumetone
  • Nabumetonum
External IDs
BRL 14777
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NabumetoneTablet500 mgOralSanis Health Inc2010-02-162017-02-08Canada
NabumetoneTablet500 mgOralAa Pharma Inc1998-08-21Not applicableCanada
Nabumetone-500Tablet500 mgOralPro Doc Limitee2008-04-072010-07-13Canada
RelafenTablet, film coated500 mg/1OralGlaxosmithkline Inc2006-02-012011-02-11Us
RelafenTablet, film coated750 mg/1OralGlaxosmithkline Inc2006-02-022011-02-11Us
Relafen Tablets 500mgTablet500 mgOralGlaxosmithkline Inc1994-12-312006-02-13Canada
Relafen Tablets 750mgTablet750 mgOralGlaxosmithkline Inc1998-01-292006-02-13Canada
Sandoz NabumetoneTablet500 mgOralSandoz Canada Incorporated2002-02-212008-08-07Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mylan-nabumetoneTablet500 mgOralMylan Pharmaceuticals2002-02-202017-01-09Canada
NabumetoneTablet, film coated750 mg/1OralProficient Rx LP2011-06-13Not applicableUs
NabumetoneTablet, film coated750 mg/1OralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc2008-03-01Not applicableUs
NabumetoneTablet500 mg/1OralBlenheim Pharmacal, Inc.2010-03-24Not applicableUs
NabumetoneTablet500 mg/1OralRemedy Repack2016-02-102017-02-07Us
NabumetoneTablet750 mg/1OralPar Pharmaceutical2003-01-24Not applicableUs
NabumetoneTablet, film coated750 mg/1OralNorthwind Pharmaceuticals2014-10-28Not applicableUs
NabumetoneTablet, film coated750 mg/1OralUnit Dose Services2008-03-01Not applicableUs50436 633420180913 8702 lkfwo9
NabumetoneTablet, film coated500 1/1OralApotex Corporation2011-12-302012-01-01Us
NabumetoneTablet, film coated750 mg/1Oralbryant ranch prepack2008-03-01Not applicableUs63629 268220180913 8702 1xh8q5z
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
NuDroxiPAK N-500Nabumetone (500 mg/1) + Capsaicin (0.25 mg/1mL) + Levomenthol (60 mg/1mL) + Methyl salicylate (250 mg/1mL)KitNucare Pharmaceuticals,inc.2018-03-16Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
RelafenNabumetone (500 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.1993-05-122011-05-31Us
International/Other Brands
Arthaxan (SmithKline Beecham (Germany; discontinued)) / Balmox (Beecham (Portugal), Meda (Switzerland)) / Dolsinal (Ferrer (Spain; discontinued)) / Listran (Uriach (Spain)) / Mebutan (Meda (Netherlands)) / Nabuser (Geymonat (Italy)) / Relafen (GlaxoSmithKline (Canada, USA; discontinued)) / Relif (Meda (Spain)) / Relifen (Sanwa (Japan), GSK (South Africa)) / Relifex (Meda (Czeck Republic, Denmark, Finland, Germany, Greece, Hungary, Ireland, Italy, Norway, Sweden, United Kingdom), GSK (Israel, Mexico, Poland, Thailand, Turkey), SmithKline Beecham (Philippines))
Categories
UNII
LW0TIW155Z
CAS number
42924-53-8
Weight
Average: 228.2863
Monoisotopic: 228.115029756
Chemical Formula
C15H16O2
InChI Key
BLXXJMDCKKHMKV-UHFFFAOYSA-N
InChI
InChI=1S/C15H16O2/c1-11(16)3-4-12-5-6-14-10-15(17-2)8-7-13(14)9-12/h5-10H,3-4H2,1-2H3
IUPAC Name
4-(6-methoxynaphthalen-2-yl)butan-2-one
SMILES
COC1=CC2=C(C=C1)C=C(CCC(C)=O)C=C2

Pharmacology

Indication

For acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis.

Associated Conditions
Pharmacodynamics

Nabumetone is a naphthylalkanone. Is is a non-selective prostaglandin G/H synthase (a.k.a. cyclooxygenase or COX) inhibitor that acts on both prostaglandin G/H synthase 1 and 2 (COX-1 and -2). Prostaglandin G/H synthase catalyzes the conversion of arachidonic acid to prostaglandin G2 and prostaglandin G2 to prostaglandin H2. Prostaglandin H2 is the precursor to a number of prostaglandins involved in fever, pain, swelling, inflammation, and platelet aggregation. The parent compound is a prodrug that undergoes hepatic biotransformation to the active compound, 6-methoxy-2-naphthylacetic acid (6MNA). The analgesic, antipyretic and anti-inflammatory effects of NSAIDs occur as a result of decreased prostaglandin synthesis.

Mechanism of action

The parent compound is a prodrug, which undergoes hepatic biotransformation to the active component, 6-methoxy-2-naphthylacetic acid (6MNA), that is a potent inhibitor of prostaglandin synthesis, most likely through binding to the COX-2 and COX-1 receptors.

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Human
UProstaglandin G/H synthase 1
inhibitor
Human
Absorption

Well absorbed from the gastrointestinal tract. Coadministration of food increases the rate of absorption and subsequent appearance of 6MNA (the active metabolite) in the plasma but does not affect the extent of conversion of nabumetone into 6MNA.

Volume of distribution
Not Available
Protein binding

The active metabolite, 6MNA, is more than 99% bound to plasma proteins.

Metabolism

Undergoes rapid biotransformation to the principal active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA). Approximately 35% of a 1000 mg oral dose of nabumetone is converted to 6MNA and 50% is converted into unidentified metabolites which are subsequently excreted in the urine.

Route of elimination

Approximately 35% of a 1000 mg oral dose of nabumetone is converted to 6MNA and 50% is converted into unidentified metabolites which are subsequently excreted in the urine.

Half life

Approximately 23 hours for the active metabolite, 6MNA. Increased in patients with renal insufficiency.

Clearance
  • 20 - 30 mL/min
Toxicity

The one overdose occurred in a 17-year-old female patient who had a history of abdominal pain and was hospitalized for increased abdominal pain following ingestion of 30 nabumetone tablets (15 grams total). Stools were negative for occult blood and there was no fall in serum hemoglobin concentration. The patient had no other symptoms.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Nabumetone Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of gastrointestinal bleeding can be increased when Nabumetone is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of gastrointestinal bleeding can be increased when Nabumetone is combined with (S)-Warfarin.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Nabumetone is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazoleThe risk or severity of hypertension can be increased when Nabumetone is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of hypertension can be increased when Nabumetone is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of hypertension can be increased when Nabumetone is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Nabumetone.
3,4-MethylenedioxyamphetamineThe risk or severity of hypertension can be increased when Nabumetone is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of hypertension can be increased when Nabumetone is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of gastrointestinal bleeding can be increased when Nabumetone is combined with 4-hydroxycoumarin.
Food Interactions
  • Avoid alcohol.
  • Take with food for faster absorption.

References

Synthesis Reference

Brian F. Becnel, Mahmood Sabahi, Kevin J. Theriot, "Production of nabumetone or precursors thereof." U.S. Patent US5907069, issued December, 1985.

US5907069
General References
Not Available
External Links
Human Metabolome Database
HMDB0014604
KEGG Drug
D00425
PubChem Compound
4409
PubChem Substance
46507729
ChemSpider
4256
BindingDB
40128
ChEBI
7443
ChEMBL
CHEMBL1070
Therapeutic Targets Database
DAP000735
PharmGKB
PA450572
HET
NBO
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Nabumetone
ATC Codes
M01AX01 — Nabumetone
AHFS Codes
  • 28:08.04.92 — Other Nonsteroidal Antiimflammatory Agents
PDB Entries
3taj / 6ci6
FDA label
Download (322 KB)
MSDS
Download (29.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers2
1CompletedTreatmentHealthy Volunteers2
4Unknown StatusTreatmentKnee Osteoarthritis (Knee OA)1
Not AvailableCompletedTreatmentKnee Osteoarthritis (Knee OA)1

Pharmacoeconomics

Manufacturers
  • Actavis elizabeth llc
  • Copley pharmaceutical inc
  • Dr reddys laboratories ltd
  • Invagen pharmaceuticals inc
  • Matrix laboratories ltd
  • Par pharmaceutical
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Smithkline beecham corp dba glaxosmithkline
Packagers
  • Altura Pharmaceuticals Inc.
  • Amerisource Health Services Corp.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Blenheim Pharmacal
  • Bryant Ranch Prepack
  • Cardinal Health
  • Caremark LLC
  • Corepharma LLC
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Doctor Reddys Laboratories Ltd.
  • Eon Labs
  • Glenmark Generics Ltd.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • InvaGen Pharmaceuticals Inc.
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prescription Dispensing Service Inc.
  • Quality Care
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Sandoz
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
TabletOral500 mg/1
TabletOral750 mg/1
Tablet, film coatedOral500 1/1
Tablet, film coatedOral750 1/1
Tablet, film coatedOral750 mg/1
Kit
Tablet, film coatedOral500 mg/1
TabletOral500 mg
TabletOral750 mg
Prices
Unit descriptionCostUnit
Relafen 750 mg tablet2.91USD tablet
Relafen 500 mg tablet2.82USD tablet
Nabumetone 750 mg tablet1.56USD tablet
Nabumetone 500 mg tablet1.32USD tablet
Apo-Nabumetone 500 mg Tablet0.39USD tablet
Mylan-Nabumetone 500 mg Tablet0.39USD tablet
Novo-Nabumetone 500 mg Tablet0.39USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPractically insolubleNot Available
logP3.08ADLARD,M ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.00193 mg/mLALOGPS
logP3.41ALOGPS
logP3.22ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)19.59ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area26.3 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity68.43 m3·mol-1ChemAxon
Polarizability26.17 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9401
Caco-2 permeable+0.9049
P-glycoprotein substrateSubstrate0.5
P-glycoprotein inhibitor INon-inhibitor0.5653
P-glycoprotein inhibitor IIInhibitor0.5656
Renal organic cation transporterNon-inhibitor0.7143
CYP450 2C9 substrateNon-substrate0.7664
CYP450 2D6 substrateNon-substrate0.7329
CYP450 3A4 substrateSubstrate0.614
CYP450 1A2 substrateInhibitor0.959
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.8591
CYP450 3A4 inhibitorNon-inhibitor0.8235
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6443
Ames testNon AMES toxic0.8942
CarcinogenicityNon-carcinogens0.8745
BiodegradationNot ready biodegradable0.8489
Rat acute toxicity1.7384 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7536
hERG inhibition (predictor II)Non-inhibitor0.8059
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-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/MSsplash10-00di-0900000000-6b7de93b51a79132630f
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-0900000000-af6f3d0d1c5f77f47279
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00fr-2900000000-53d7d6dc809a154d16c2

Taxonomy

Description
This compound belongs to the class of organic compounds known as naphthalenes. These are compounds containing a naphthalene moiety, which consists of two fused benzene rings.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Naphthalenes
Sub Class
Not Available
Direct Parent
Naphthalenes
Alternative Parents
Anisoles / Alkyl aryl ethers / Ketones / Organic oxides / Hydrocarbon derivatives
Substituents
Naphthalene / Anisole / Alkyl aryl ether / Ketone / Ether / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound / Carbonyl group
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
methyl ketone, methoxynaphthalene (CHEBI:7443)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Fackovcova D, Kristova V, Kriska M: Renal damage induced by the treatment with non-opioid analgesics--theoretical assumption or clinical significance. Bratisl Lek Listy. 2000;101(8):417-22. [PubMed:11153163]
  2. Roy HK, Karolski WJ, Ratashak A: Distal bowel selectivity in the chemoprevention of experimental colon carcinogenesis by the non-steroidal anti-inflammatory drug nabumetone. Int J Cancer. 2001 May 15;92(4):609-15. [PubMed:11304699]
  3. van Kraaij DJ, Hovestad-Witterland AH, de Metz M, Vollaard EJ: A comparison of the effects of nabumetone vs meloxicam on serum thromboxane B2 and platelet function in healthy volunteers. Br J Clin Pharmacol. 2002 Jun;53(6):644-7. [PubMed:12047490]
  4. Hedner T, Samulesson O, Wahrborg P, Wadenvik H, Ung KA, Ekbom A: Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis. Drugs. 2004;64(20):2315-43; discussion 2344-5. [PubMed:15456329]
  5. Elliott SN, McKnight W, Cirino G, Wallace JL: A nitric oxide-releasing nonsteroidal anti-inflammatory drug accelerates gastric ulcer healing in rats. Gastroenterology. 1995 Aug;109(2):524-30. [PubMed:7615202]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Giuliano F, Ferraz JG, Pereira R, de Nucci G, Warner TD: Cyclooxygenase selectivity of non-steroid anti-inflammatory drugs in humans: ex vivo evaluation. Eur J Pharmacol. 2001 Aug 24;426(1-2):95-103. [PubMed:11525777]
  2. Takeuchi K, Smale S, Premchand P, Maiden L, Sherwood R, Thjodleifsson B, Bjornsson E, Bjarnason I: Prevalence and mechanism of nonsteroidal anti-inflammatory drug-induced clinical relapse in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2006 Feb;4(2):196-202. [PubMed:16469680]
  3. Cipollone F, Ganci A, Panara MR, Greco A, Cuccurullo F, Patrono C, Patrignani P: Effects of nabumetone on prostanoid biosynthesis in humans. Clin Pharmacol Ther. 1995 Sep;58(3):335-41. [PubMed:7554708]
  4. Bensen W, Zizzo A: Newer, safer nonsteroidal anti-inflammatory drugs. Rational NSAID selection for arthritis. Can Fam Physician. 1998 Jan;44:101-2, 105-7. [PubMed:9481468]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Peroxidase activity
Specific Function
Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production o...
Gene Name
MPO
Uniprot ID
P05164
Uniprot Name
Myeloperoxidase
Molecular Weight
83867.71 Da
References
  1. Saleh TS, Calixto JB, Medeiros YS: Effects of anti-inflammatory drugs upon nitrate and myeloperoxidase levels in the mouse pleurisy induced by carrageenan. Peptides. 1999;20(8):949-56. [PubMed:10503773]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Data supporting this enzyme action are limited to one in vitro study.
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. Turpeinen M, Hofmann U, Klein K, Murdter T, Schwab M, Zanger UM: A predominate role of CYP1A2 for the metabolism of nabumetone to the active metabolite, 6-methoxy-2-naphthylacetic acid, in human liver microsomes. Drug Metab Dispos. 2009 May;37(5):1017-24. doi: 10.1124/dmd.108.025700. Epub 2009 Feb 9. [PubMed:19204080]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 23:30