Identification

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

Nabumetone was originally developed as a non-acidic non-steroidal anti-inflammatory drug (NSAID).Label It was thought to avoid trapping of the drug in the stomach by making it unable to dissociate into ions which was believed to reduce GI toxicity by limiting local action.8 While slightly reduced, possibly due to a degree of cyclooxygenase-2 selectivity (COX-2), nabumetone still produces significant adverse effects in the GI tract.Label,1 The molecule itself is a pro-drug with its 6-methoxy-2-naphthylacetic acid (6-MNA) metabolite acting as a potent COX inhibitor similar in structure to naproxen. Nabumetone was developed by Smithkline Beecham under the trade name Relafen and first received FDA approval in December, 1991.12

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 / BRL-14777
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NabumetoneTablet500 mgOralAa Pharma Inc1998-08-21Not applicableCanada
NabumetoneTablet500 mgOralSanis Health Inc2010-02-162017-02-08Canada
Nabumetone-500Tablet500 mgOralPro Doc Limitee2008-04-072010-07-13Canada
RelafenTablet, film coated500 mg/1OralGlaxosmithkline Inc2006-02-012011-02-11Us
RelafenTablet, film coated500 mg/1OralPhysicians Total Care, Inc.1993-05-122011-05-31Us
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
Additional Data Available
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    Application Number

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  • Product Code
    Product Code

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mylan-nabumetoneTablet500 mgOralMylan Pharmaceuticals2002-02-202017-01-09Canada
NabumetoneTablet, film coated750 mg/1OralPD-Rx Pharmaceuticals, Inc.2008-03-01Not applicableUs
NabumetoneTablet, film coated500 mg/1Oralbryant ranch prepack2008-03-01Not applicableUs
NabumetoneTablet, film coated500 mg/1OralTeva2001-08-202018-06-30Us00093 1015 01 nlmimage10 a929d4fe
NabumetoneTablet, film coated500 mg/1OralA-S Medication Solutions2008-03-01Not applicableUs50090 153120180907 15195 1vmm1nu
NabumetoneTablet, film coated500 mg/1OralDispensing Solutions, Inc.2008-03-01Not applicableUs
NabumetoneTablet, film coated750 mg/1OralPD-Rx Pharmaceuticals, Inc.2001-09-26Not applicableUs
NabumetoneTablet, film coated750 mg/1OralNucare Pharmaceuticals, Inc.2008-03-01Not applicableUs
NabumetoneTablet, film coated750 mg/1OralRxchange Co2014-11-13Not applicableUs
NabumetoneTablet, film coated750 mg/1OralProficient Rx LP2011-06-13Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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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)) / 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

Indicated for:Label

1) Symptomatic relief in rheumatoid arthritis.

2) Symptomatic relief in osteoarthritis.

Associated Conditions
Pharmacodynamics

NSAIDs, like nabumetone, are well established as analgesics. NSAIDs reduce both peripheral and central sensitization of nociceptive neurons due to inflammation which contribute to hyperalgesia and allodynia.9,6 This sensitization occurs through reducing the action potential threshold in peripheral neurons, reducing the intensity of painful stimuli needed to produce a painful sensation. Centrally, activation of dorsal horn neurons occurs along with increased release of glutamate, calcitonin gene-related peptide (CGRP), and substance P which increase the transmission of painful stimuli. Coupled with this is an inhibition glycinergic neurons which normally inhibit pain transmission, a phenomenon known as disinhibition. Increased activity ofn-methyl d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors leads to the establishment of central sensitization, allowing both mild painful and innocuous stimuli to produce action potentials in nociceptive projection neurons. NSAIDs are effective in reducing mild-moderate acute and chronic nociceptive pain, however, the usefulness of NSAIDs in neuropathic pain is limited.

The anti-inflammatory effect of NSAIDs is mediated by preventing vasodilation, increases in vascular permeability, and the release of cytokines from endothelial cells.9,7 These three effects together prevent immunocompetent cells from migrating to the site of injury thereby preventing additional damage and inflammation due to activation of the immune system at the site of damage. PGs also modulate T-helper cell activation and differentiation, an activity which is thought to be of importance in arthritic conditions.

The anti-pyretic effect of NSAIDs is mediated through preventing increases in temperature by prostaglandins (PGs) via the hypothalamus.9 Activation of this process by other inflammatory mediators relies upon subsequent action by PGs, therefore NSAIDs are able to reduce fever due to these mediators as well.

The adverse effects of NSAIDs are related to their therapeutic effects.9 The same vasodilatory action which occurs in inflammation also serves to regulate blood flow to the kidneys through the afferent renal arteries. NSAIDs are widely known as nephrotoxic agents as the reduction in PGs produces vasoconstriction of these arteries resulting in reduced blood flow to the kidneys and a subsequent decline in renal function. Reductions in mucus and HCO3- secretion in the stomach increases the risk of ulceration by limiting the protection mediated by PGs. Lastly, COX-2 selective agents like nabumetone can unbalance prothrombotic and antithrombotic prostanoid generation leading to increased platelet aggregation and increased risk of thrombosis.

Mechanism of action

Nabumetone's active metabolite, 6-MNA, is an inhibitor of both COX-1 and COX-2 although it exhibits some COX-2 selectivity.Label,1 Inhibition of COX-1 and COX-2 reduces conversion of arachidonic acid to PGs and thromboxane (TXA2). This reduction in prostanoid production is the common mechanism that mediates the effects of nambutone.

PGE2 is the primary PG involved in modulation of nociception.6 It mediates peripheral sensitization through a variety of effects.9,6 PGE2 activates the Gq-coupled EP1 receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE2 also activates the EP4 receptor, coupled to Gs, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE2 act via EP3 to increase sensitivity to bradykinin and via EP2 to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP2 receptor which couples to Gs. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGI2 is known to play a role via its Gs-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain.

PGI2 and PGE2 contribute to acute inflammation via their IP and EP2 receptors.9,7 Similarly to β adrenergic receptors these are Gs-coupled and mediate vasodilation through the AC/PKA pathway. PGE2 also contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury.9 PGD2 plays a role in the activation of endothelial cell release of cytokines through its DP1 receptor.7 PGI2 and PGE2 modulate T-helper cell activation and differentiation through IP, EP2, and EP4 receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation.

PGE2 can cross the blood-brain barrier and act on excitatory Gq EP3 receptors on thermoregulatory neurons in the hypothalamus.9 This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE2 thereby reducing the activity of these neurons.

The adverse effects of NSAIDs stem from the protective and regulatory roles of prostanoids which have been well-characterized.9 PGI2 and PGE2 regulate blood flow to the kidney by similar mechanisms to the vasodilation they produce in inflammation. Prevention of this regulation by NSAIDs produces vasoconstriction which limits renal function by reducing blood flow and the hydrostatic pressure which drives filtration. PGE2 also regulates gastric protection via EP3 receptors which are, in this location, coupled to Gi which inhibits the AC/PKA pathway. This reduces the secretion of protons by H+/K+ ATPase in parietal cells and increases the secretion of mucus and HCO3- by superficial endothelial cells. Disruption of this protective action by NSAIDs lead to ulceration of the gastric mucosa. Lastly, disruption of PGI2, which opposes platelet aggregation, generation by COX-2 selective agents leads to an imbalance with TXA2 generated by COX-1, which promotes aggregation of platelets, leading to increased risk of thrombosis. Since nabumetone is somewhat COX-2 selective it is thought to promote this imbalance and increase thrombotic risk.1

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Humans
UProstaglandin G/H synthase 1
inhibitor
Humans
Additional Data Available
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Contraindications

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Absorption

Nabumetone is well-absorbed from the GI tract and undergoes significant first pass metabolism resulting in approximately 35% being converted to the active metabolite, 6-MNA.Label,1 Tmax for 6-MNA varies widely with a mean values of 3 and 11 hours reported in official product monographs, and described as 9-12 hours in published literature Label,10,1 Administration with food increases Cmax by 33% and increases absorption rate.Label,1 If formulated as a suspension the Cmax increases and the Tmax is reduced by 0.8 hours while the all other pharmacokinetic parameters remain unchanged.1

Volume of distribution

The Vd of 6-MNA reported after administration of a single dose is 0.1-0.2 L/kg or approximately 5-10 L.1 Vdss reported in official product labeling is approximately 53 L.Label,10

Protein binding

6-MNA is over 99% bound to plasma proteins, likely albumin.Label,1 The unbound fraction is 0.1-0.2% and remains proportional in the dose range of 1000-2000mg

Metabolism

Nabumetone is reduced to 3-hydroxy nabumetone by the aldo-keto reductase-1C family and by corticosteroid 11-beta-dehydrogenase2,3. It then undergoes oxidative cleavage by CYP1A2 to 6-MNA, the active metabolite.4,3 6-MNA is eliminated by O-demethylation by CYP2C9 to 6-hydroxy-2-naphthylacetic acid (6-HNA).2,3 Both 6-MNA and 6-HNA are further converted to conjugates.3 Other metabolites are generated through a mix of ketone reduction and O-demethylation along with subsequent conjugation. Glucuronide conjugates of several metabolites have been found to become further conjugated to glycine residues.5

Route of elimination

Most drug is eliminated via hepatic metabolism with minimal to no parent drug detectable in the plasma.Label,1 80% of the dose is then excreted by the kidneys and 10% in the feces. It does not appear to undergo enterohepatic recirculation.

Half life

6-MNA has a mean half-life of 24 hours with a range of 19-36 hours.Label

Clearance

6-MNA has an apparent steady-state clearance of 20 - 30 mL/min.Label

Toxicity

LD50 Values

Mouse: 4290 mg/kg (Oral), 2380 mg/kg (IP)11

Rat: 3880 mg/kg (Oral), 1520 mg/kg (IP), >10 g/kg (SC)11

Monkey: 3200 mg/kg (Oral)11

Overdose

Signs and symptoms of nabumetone overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain.Label These are considered reversible with supportive care. GI bleeding, hypertension, acute kidney injury, respiratory depression, and coma are rare but can occur. No antidote exists for nabumetone overdose although administration of activated charcoal and/or induction of emesis can reduce absorption if the nabumetone dose was taken less than 4 hours prior.Label,10 6-MNA is cannot be cleared by dialysis.

Carcinogenicity & Mutagenicity

Nabumetone was not significantly carcinogenic in rats or mice studied over 2 years.Label Neither the Ames test nor mouse micronucleus test showed nabumetone or it's active metabolite, 6-MNA, to be mutagenic. Chromosomal abberation has been observed in cultured lymphocytes exposed to concentrations of 80 mcg/mL and higher of nabumetone or 6-MNA equivalent to the maximum recommended human dose.

Reproductive Toxicity

No adverse effects on fertility have been observed in male and female rats at doses of 320 mg/kg/day.Label,10] No teratogenicity has been observed in pregnant rabbits or rats. Dystocia and delayed parturition have been noted in rats resulting in reduced survival of offspring. This has been attributed to the role of prostaglandins in uterine contraction. NSAIDs can also cause premature closure of the ductus ateriosus.

Lactation

6-MNA has been detected in the milk of lactating rats.Label,10 While no data is available in humans, 6-MNA is both highly protein bound and exists in its anionic form in circulation. For these reasons partitioning into breast milk is expected to be limited.

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.
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.
4-MethoxyamphetamineThe risk or severity of hypertension can be increased when Nabumetone is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of hypertension can be increased when Nabumetone is combined with 5-methoxy-N,N-dimethyltryptamine.
Additional Data Available
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  • Severity
    Severity

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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
  1. Davies NM: Clinical pharmacokinetics of nabumetone. The dawn of selective cyclo-oxygenase-2 inhibition? Clin Pharmacokinet. 1997 Dec;33(6):404-16. doi: 10.2165/00003088-199733060-00001. [PubMed:9435990]
  2. Matsumoto K, Hasegawa T, Koyanagi J, Takahashi T, Akimoto M, Sugibayashi K: Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):127-35. doi: 10.1007/s13318-014-0190-0. [PubMed:24659525]
  3. Nobilis M, Mikusek J, Szotakova B, Jirasko R, Holcapek M, Chamseddin C, Jira T, Kucera R, Kunes J, Pour M: Analytical power of LLE-HPLC-PDA-MS/MS in drug metabolism studies: identification of new nabumetone metabolites. J Pharm Biomed Anal. 2013 Jun;80:164-72. doi: 10.1016/j.jpba.2013.03.006. Epub 2013 Mar 19. [PubMed:23584048]
  4. 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]
  5. Ceslova L, Holcapek M, Nobilis M: Identification of combined conjugation of nabumetone phase I metabolites with glucuronic acid and glycine in minipig biotransformation using coupling high-performance liquid chromatography with electrospray ionization mass spectrometry. J Pharm Biomed Anal. 2014 Jan;88:221-4. doi: 10.1016/j.jpba.2013.08.053. Epub 2013 Sep 12. [PubMed:24083957]
  6. Chen L, Yang G, Grosser T: Prostanoids and inflammatory pain. Prostaglandins Other Lipid Mediat. 2013 Jul-Aug;104-105:58-66. doi: 10.1016/j.prostaglandins.2012.08.006. Epub 2012 Sep 3. [PubMed:22981510]
  7. Hirata T, Narumiya S: Prostanoids as regulators of innate and adaptive immunity. Adv Immunol. 2012;116:143-74. doi: 10.1016/B978-0-12-394300-2.00005-3. [PubMed:23063076]
  8. Blower PR: The unique pharmacologic profile of nabumetone. J Rheumatol Suppl. 1992 Nov;36:13-9. [PubMed:1474529]
  9. Emer M. Smyth; Tilo Grosser; Garret A. FitzGerald (2018). 37 & 38. In Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education. [ISBN:978-1-25-958473-2]
  10. Nabumetone Health Canada Monograph [Link]
  11. ChemIDplus: Nabumetone [Link]
  12. FDA: Relafen [Link]
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
Wikipedia
Nabumetone
ATC Codes
M01AX01 — Nabumetone
AHFS Codes
  • 28:08.04.92 — Other Nonsteroidal Antiimflammatory Agents
PDB Entries
3taj / 6ci6
FDA label
Download (243 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 mg/1
Tablet, film coatedOral750 1/1
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
melting point (°C)78-82Health Canada Product Monograph, AA Pharma Inc.
water solubilityPractically insolubleFDA Label, Eon Labs Inc.
logP2400FDA Label, Eon Labs Inc.
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
Humans
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
Humans
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
Humans
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
Humans
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]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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. Matsumoto K, Nemoto E, Hasegawa T, Akimoto M, Sugibayashi K: In vitro characterization of the cytochrome P450 isoforms involved in the metabolism of 6-methoxy-2-napthylacetic acid, an active metabolite of the prodrug nabumetone. Biol Pharm Bull. 2011;34(5):734-9. [PubMed:21532165]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
11-beta-hydroxysteroid dehydrogenase [nad(p)] activity
Specific Function
Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the rea...
Gene Name
HSD11B1
Uniprot ID
P28845
Uniprot Name
Corticosteroid 11-beta-dehydrogenase isozyme 1
Molecular Weight
32400.665 Da
References
  1. Matsumoto K, Hasegawa T, Koyanagi J, Takahashi T, Akimoto M, Sugibayashi K: Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):127-35. doi: 10.1007/s13318-014-0190-0. [PubMed:24659525]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function
Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the in...
Gene Name
AKR1C1
Uniprot ID
Q04828
Uniprot Name
Aldo-keto reductase family 1 member C1
Molecular Weight
36788.02 Da
References
  1. Matsumoto K, Hasegawa T, Koyanagi J, Takahashi T, Akimoto M, Sugibayashi K: Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):127-35. doi: 10.1007/s13318-014-0190-0. [PubMed:24659525]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function
Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2....
Gene Name
AKR1C3
Uniprot ID
P42330
Uniprot Name
Aldo-keto reductase family 1 member C3
Molecular Weight
36852.89 Da
References
  1. Matsumoto K, Hasegawa T, Koyanagi J, Takahashi T, Akimoto M, Sugibayashi K: Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):127-35. doi: 10.1007/s13318-014-0190-0. [PubMed:24659525]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Retinal dehydrogenase activity
Specific Function
Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Also has some 20-alpha-hydroxysteroid...
Gene Name
AKR1C4
Uniprot ID
P17516
Uniprot Name
Aldo-keto reductase family 1 member C4
Molecular Weight
37066.52 Da
References
  1. Matsumoto K, Hasegawa T, Koyanagi J, Takahashi T, Akimoto M, Sugibayashi K: Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes. Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):127-35. doi: 10.1007/s13318-014-0190-0. [PubMed:24659525]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Davies NM: Clinical pharmacokinetics of nabumetone. The dawn of selective cyclo-oxygenase-2 inhibition? Clin Pharmacokinet. 1997 Dec;33(6):404-16. doi: 10.2165/00003088-199733060-00001. [PubMed:9435990]

Drug created on June 13, 2005 07:24 / Updated on June 16, 2019 06:44