NABUMETONE

First approved in 1991

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H16O2
Molecular Weight	228.2869
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)CCc1ccc2cc(ccc2c1)OC

InChI

InChIKey=BLXXJMDCKKHMKV-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00461
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/cdi/nabumetone.html

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. 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. Nabumetone is used for acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis. Nabumetone has been developed by Beecham. It is available under numerous brand names, such as Relafen, Relifex, and Gambaran.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase-1 124 Target ID: CHEMBL221 Sources: http://www.drugbank.ca/drugs/DB00461	Inhibitor 7728		149.0 µM [IC50]
Cyclooxygenase-2 189 Target ID: CHEMBL230 Sources: http://www.drugbank.ca/drugs/DB00461	Inhibitor 7728		230.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Osteoarthritis 151 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2000/75-189_Nabumetone_prntlbl.pdf	Primary		Approved 8043	Nabumetone Approved Use Nabumetone tablets are indicated for relief of signs and symptoms of osteoarthritis and rheumatoid arthritis. Launch Date 9.5921281E11
Rheumatoid arthritis 294 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2000/75-189_Nabumetone_prntlbl.pdf	Primary		Approved 8043	Nabumetone Approved Use Nabumetone tablets are indicated for relief of signs and symptoms of osteoarthritis and rheumatoid arthritis. Launch Date 9.5921281E11

C_max

Value	Dose	Analyte	Population
52.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
66.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
33.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.48 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12763542/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	NABUMETONE plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1022 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1270 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1120 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2150 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
204.98 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12763542/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	NABUMETONE plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
27.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
34.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
26.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
38.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2744071/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	6-METHOXY-2-NAPHTHYLACETIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.82 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12763542/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	NABUMETONE plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 g 1 times / day steady, oral (max) Recommended Dose: 2 g, 1 times / day Route: oral Route: steady Dose: 2 g, 1 times / day Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9	unhealthy, adult n = 1677 Health Status: unhealthy Condition: rheumatoid arthritis and osteoarthritis Age Group: adult Sex: unknown Population Size: 1677 Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9	Disc. AE: Diarrhea, Dyspepsia... AEs leading to discontinuation/dose reduction: Diarrhea (1.3%) Dyspepsia (0.8%) Abdominal pain (1.1%) Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9

AEs

AE	Significance	Dose	Population
Dyspepsia	0.8% Disc. AE	2 g 1 times / day steady, oral (max) Recommended Dose: 2 g, 1 times / day Route: oral Route: steady Dose: 2 g, 1 times / day Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9	unhealthy, adult n = 1677 Health Status: unhealthy Condition: rheumatoid arthritis and osteoarthritis Age Group: adult Sex: unknown Population Size: 1677 Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9
Abdominal pain	1.1% Disc. AE	2 g 1 times / day steady, oral (max) Recommended Dose: 2 g, 1 times / day Route: oral Route: steady Dose: 2 g, 1 times / day Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9	unhealthy, adult n = 1677 Health Status: unhealthy Condition: rheumatoid arthritis and osteoarthritis Age Group: adult Sex: unknown Population Size: 1677 Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9
Diarrhea	1.3% Disc. AE	2 g 1 times / day steady, oral (max) Recommended Dose: 2 g, 1 times / day Route: oral Route: steady Dose: 2 g, 1 times / day Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9	unhealthy, adult n = 1677 Health Status: unhealthy Condition: rheumatoid arthritis and osteoarthritis Age Group: adult Sex: unknown Population Size: 1677 Sources: https://www.aapharma.ca/downloads/en/PIL/2018/00042393-Nabumetone_PM__en.pdf Page: 9

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1601	substrate 936	substrate 1118

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2B6 616 CYP2C19 910 CYP2E1 606 CYP2A6 485 CYP2C8 634 CYP3A5 367 CYP1A1 325 alcohol dehydrogenase 6 ALDH 5 FMO1 16 FMO3 64 11-beta-HSD 3 AKR1C4 5 AKR1C1 18 AKR1C2 8

Drug as victim

Target	Modality	Activity	Metabolite
CYP2A6 485	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	no
FMO1 16	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	no
FMO3 64	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	no
CYP2C8 634	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
CYP2C9 936	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
CYP3A4 1601	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
CYP3A5 367	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/33146575/	weak
11-beta-HSD 3	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
AKR1C1 18	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
AKR1C2 8	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
AKR1C4 5	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/24659525/	yes
ALDH 5	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/31855101/	yes	6-MN-CHO 1
CYP1A1 325	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2B6 616	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2C19 910	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2D6 1118	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
CYP2E1 606	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/19204080/	yes
alcohol dehydrogenase 6	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/31855101/	yes	6-MNE-ol 1

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7443	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7443
ChemicalBook	CB2386779	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2386779
MolPort	MolPort-001-793-710	https://www.molport.com/shop/molecule-link/MolPort-001-793-710
Selleck Chemicals	nabumetone	http://www.selleckchem.com/products/nabumetone.html
ZINC	ZINC000000020221	http://zinc15.docking.org/substances/ZINC000000020221
eMolecules	592792	https://www.emolecules.com/cgi-bin/more?vid=592792

PubMed

Title	Date	PubMed
Comparative biotransformation and disposition studies of nabumetone in humans and minipigs using high-performance liquid chromatography with ultraviolet, fluorescence and mass spectrometric detection.	2003 Aug 8	12899954
Safe full-dose one-step nabumetone challenge in patients with nonsteroidal anti-inflammatory drug hypersensitivity.	2003 Jul-Aug	12974196
Analysis of nabumetone in human plasma by HPLC. Application to single dose pharmacokinetic studies.	2003 Jun 1	12763542
Risk of cancer in a large cohort of nonaspirin NSAID users: a population-based study.	2003 Jun 2	12771981
[Meta-analysis on the effect and adverse reaction on patients with osteoarthritis and rheumatoid arthritis treated with non-steroidal anti-inflammatory drugs].	2003 Nov	14687510
Selective COX-2 inhibition and cardiovascular effects: a review of the rofecoxib development program.	2003 Oct	14564311
Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis.	2004	15456329
Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin.	2004	15132714
Risk of breast cancer among users of aspirin and other anti-inflammatory drugs.	2004 Aug 2	15226764
Application of pentafluorophenyl hydrazine derivatives to the analysis of nabumetone and testosterone in human plasma by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.	2004 Dec	15700167
In vitro investigation of the effects of nonsteroidal anti-inflammatory drugs, prostaglandin E2, and prostaglandin F2alpha on contractile activity of the third compartment of the stomach of llamas.	2004 Feb	14974580
General principles of pharmaceutical solid polymorphism: a supramolecular perspective.	2004 Feb 23	14962581
Incremental cost-effectiveness of cyclooxygenase 2-selective versus nonselective nonsteroidal anti-inflammatory drugs in a cohort of coumarin users: a pharmacoeconomic analysis linked to a case-control study.	2004 Jul	15336481
Regulation of metalloproteinases and NF-kappaB activation in rabbit synovial fibroblasts via E prostaglandins and Erk: contrasting effects of nabumetone and 6MNA.	2004 Jul	15210577
Adverse effect of drug-induced emotional problems on work and daily activities. A principal component as an independent predictor of ADRs in Shanghai patients with osteo-arthropathy taking nabumetone.	2004 Jun	15222724
Risk factors of adverse drug reaction from non-steroidal anti-inflammatory drugs in Shanghai patients with arthropathy.	2004 Mar	15000891
Identification and determination of phase II nabumetone metabolites by high-performance liquid chromatography with photodiode array and mass spectrometric detection.	2004 Mar 26	15058587
Effects of dietary anticarcinogens and nonsteroidal anti-inflammatory drugs on rat gastrointestinal UDP-glucuronosyltransferases.	2004 Mar-Apr	15161036
A population based historical cohort study of the mortality associated with nabumetone, Arthrotec, diclofenac, and naproxen.	2004 May	15124256
Efficacy and safety of rofecoxib 12.5 mg versus nabumetone 1,000 mg in patients with osteoarthritis of the knee: a randomized controlled trial.	2004 May	15086644
Pain management in osteoarthritis: a focus on onset of efficacy--a comparison of rofecoxib, celecoxib, acetaminophen, and nabumetone across four clinical trials.	2004 Nov	15556830
Calculation of cyclodextrin binding affinities: energy, entropy, and implications for drug design.	2004 Nov	15339804
Systematic review: is ingestion of paracetamol or non-steroidal anti-inflammatory drugs associated with exacerbations of inflammatory bowel disease?	2004 Nov 15	15569105
[Reflections on COX, Vioxx and Relifex. Increased cardiovascular risk following selective COX-2 inhibition].	2004 Nov 25	15631229
The upper gastrointestinal safety of rofecoxib vs. NSAIDs: an updated combined analysis.	2004 Oct	15462687
Effect of the addition of water-soluble polymers on the interfacial properties of aerosol OT vesicles.	2004 Oct 15	15450468
Patient characteristics associated with outpatient prescriptions for nabumetone and oxaprozin versus celecoxib and rofecoxib.	2005 Apr 1	15790802
Simplex optimization of the variables affecting the micelle-stabilized room temperature phosphorescence of 6-methoxy-2-naphthylacetic acid and its kinetic determination in human urine.	2005 Apr 1	15766723
Photosensitizing properties of 6-methoxy-2-naphthylacetic acid, the major metabolite of the phototoxic non-steroidal anti-inflammatory and analgesic drug nabumetone.	2005 Aug	16124404
Pulp-dentine complex changes and root resorption during intrusive orthodontic tooth movement in patients prescribed nabumetone.	2005 Jan	15614010
The nonsteroidal anti-inflammatory drug, nabumetone, differentially inhibits beta-catenin signaling in the MIN mouse and azoxymethane-treated rat models of colon carcinogenesis.	2005 Jan 20	15617833
Rofecoxib for osteoarthritis.	2005 Jan 25	15654705
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Development and validation of a reversed-phase liquid chromatographic method for separation and simultaneous determination of COX-2 inhibitors in pharmaceuticals and its application to biological fluids.	2005 Jun	15627281
Subjective impact of osteoarthritis flare-ups on patients' quality of life.	2005 Mar 16	15771777
Cyclo-oxygenase 2 inhibitor, nabumetone, inhibits proliferation in chronic myeloid leukemia cell lines.	2005 May	16019514
Comparative effects of indomethacin and nabumetone on urine and electrolyte output in conscious rats.	2005 Nov	16293937
Risk of hospitalization with peptic ulcer disease or gastrointestinal hemorrhage associated with nabumetone, Arthrotec, diclofenac, and naproxen in a population based cohort study.	2005 Nov	16265705
Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population.	2005 Nov 29	16316472
Low direct cytotoxicity of nabumetone on gastric mucosal cells.	2005 Sep	16133963
Temporal relationship between use of NSAIDs, including selective COX-2 inhibitors, and cardiovascular risk.	2006	16808554
Tolerance of diclofenac after hypersensitivity to celecoxib and to nabumetone.	2006 Apr	16542210
Picture of the month. Stevens-Johnson Syndrome.	2006 Aug	16894078
Treatment of patients with osteoarthritis with rofecoxib compared with nabumetone.	2006 Feb	16484875
Prevalence and mechanism of nonsteroidal anti-inflammatory drug-induced clinical relapse in patients with inflammatory bowel disease.	2006 Feb	16469680
Evaluation of hydroxyimine as cytochrome P450-selective prodrug structure.	2006 Feb 9	16451086
NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland.	2006 Jul	16731535
Comparison of Anti-inflammatory Activities of Six Curcuma Rhizomes: A Possible Curcuminoid-independent Pathway Mediated by Curcuma phaeocaulis Extract.	2006 Jun	16786056
A systematic investigation of recovery in preparative reverse phase high performance liquid chromatography/mass spectrometry.	2006 Jun 30	16387320
Spherical agglomeration of mefenamic acid and nabumetone to improve micromeritics and solubility: a technical note.	2006 May 26	16796365

Patents

Sample Use Guides

In Vivo Use Guide

Initial dose: 1000 mg orally once a day Maintenance dose: 1500 to 2000 mg orally per day in 1 or 2 divided doses Maximum dose: 2000 mg/day

Route of Administration: Oral

In Vitro Use Guide

Nabumetone (50 ug/ml) was found to significantly increase COX-2 at mRNA levels but directly suppress the concentration of PGE2 in culture medium of human intervertebral disc cells.

Name

Type

Language

NABUMETONE

Official Name

English

NABUMETONE [VANDF]

Common Name

English

NABUMETONE [USP-RS]

Common Name

English

BRL-14777

Code

English

NABUMETONE [ORANGE BOOK]

Common Name

English

NABUMETONE [JAN]

Common Name

English

NABUMETONE [MART.]

Common Name

English

2-BUTANONE, 4-(6-METHOXY-2-NAPHTHALENYL)-

Systematic Name

English

NABUMETONE [USP]

Common Name

English

NABUMETONE [USP MONOGRAPH]

Common Name

English

NABUMETONE [MI]

Common Name

English

NABUMETONE [EP MONOGRAPH]

Common Name

English

RELAFEN

Brand Name

English

NABUMETONE [INN]

Common Name

English

4-(6-METHOXY-2-NAPHTHYL)-2-BUTANONE

Systematic Name

English

NABUMETONE [USAN]

Common Name

English

NSC-758623

Code

English

NABUMETONE [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

M01AX01