Peringatan Keamanan

LD₅₀ Values

Mouse: 4290 mg/kg (Oral), 2380 mg/kg (IP)^L6565

Rat: 3880 mg/kg (Oral), 1520 mg/kg (IP), >10 g/kg (SC)^L6565

Monkey: 3200 mg/kg (Oral)^L6565

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,L6466 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,L6466] 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,L6466 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.

Nabumetone

DB00461

small molecule approved

Deskripsi

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.^A179077 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,A178903 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.^L6568

Struktur Molekul 2D

Berat 228.2863

Wujud solid

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) 6-MNA has a mean half-life of 24 hours with a range of 19-36 hours.[label]

Volume Distribusi The Vd of 6-MNA reported after administration of a single dose is 0.1-0.2 L/kg or approximately 5-10 L.[A178903] Vdss reported in official product labeling is approximately 53 L.[label,L6466]

Klirens (Clearance) 6-MNA has an apparent steady-state clearance of 20 - 30 mL/min.[label]

Absorpsi

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,A178903 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,L6466,A178903 Administration with food increases Cmax by 33% and increases absorption rate.label,A178903 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.^A178903

Metabolisme

Nabumetone is reduced to 3-hydroxy nabumetone by the aldo-keto reductase-1C family and by corticosteroid 11-beta-dehydrogenaseA178897,A178900. It then undergoes oxidative cleavage by CYP1A2 to 6-MNA, the active metabolite.A17750,A178900 6-MNA is eliminated by O-demethylation by CYP2C9 to 6-hydroxy-2-naphthylacetic acid (6-HNA).A178897,A178900 Both 6-MNA and 6-HNA are further converted to conjugates.^A178900 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.^A178972

Rute Eliminasi

Most drug is eliminated via hepatic metabolism with minimal to no parent drug detectable in the plasma.label,A178903 80% of the dose is then excreted by the kidneys and 10% in the feces. It does not appear to undergo enterohepatic recirculation.

Interaksi Makanan

2 Data

1. Avoid alcohol. Alcohol use may aggravate the gastrointestinal irritation caused by this drug.
2. Take with food. Food increases the rate of absorption.

Interaksi Obat

1690 Data

Peginterferon alfa-2b	The serum concentration of Nabumetone can be increased when it is combined with Peginterferon alfa-2b.
Leflunomide	The serum concentration of Nabumetone can be decreased when it is combined with Leflunomide.
Teriflunomide	The serum concentration of Nabumetone can be decreased when it is combined with Teriflunomide.
Amlodipine	The metabolism of Nabumetone can be decreased when combined with Amlodipine.
Phentermine	The risk or severity of hypertension can be increased when Phentermine is combined with Nabumetone.
Midodrine	The risk or severity of hypertension can be increased when Midodrine is combined with Nabumetone.
Eletriptan	The risk or severity of hypertension can be increased when Eletriptan is combined with Nabumetone.
Isoetharine	The risk or severity of hypertension can be increased when Isoetharine is combined with Nabumetone.
Methysergide	The risk or severity of hypertension can be increased when Methysergide is combined with Nabumetone.
Cabergoline	The risk or severity of hypertension can be increased when Cabergoline is combined with Nabumetone.
Dihydroergotamine	The risk or severity of hypertension can be increased when Dihydroergotamine is combined with Nabumetone.
Methylergometrine	The risk or severity of hypertension can be increased when Methylergometrine is combined with Nabumetone.
Norepinephrine	The risk or severity of hypertension can be increased when Norepinephrine is combined with Nabumetone.
Phenylpropanolamine	The risk or severity of hypertension can be increased when Phenylpropanolamine is combined with Nabumetone.
Droperidol	The risk or severity of hypertension can be increased when Droperidol is combined with Nabumetone.
Doxapram	The risk or severity of hypertension can be increased when Nabumetone is combined with Doxapram.
Atropine	The risk or severity of hypertension can be increased when Nabumetone is combined with Atropine.
Lisuride	The risk or severity of hypertension can be increased when Nabumetone is combined with Lisuride.
Linezolid	The risk or severity of hypertension can be increased when Nabumetone is combined with Linezolid.
Metaraminol	The risk or severity of hypertension can be increased when Nabumetone is combined with Metaraminol.
Furazolidone	The risk or severity of hypertension can be increased when Nabumetone is combined with Furazolidone.
Thioridazine	The risk or severity of hypertension can be increased when Nabumetone is combined with Thioridazine.
Ergotamine	The risk or severity of hypertension can be increased when Nabumetone is combined with Ergotamine.
Nicergoline	The risk or severity of hypertension can be increased when Nabumetone is combined with Nicergoline.
Sufentanil	The risk or severity of hypertension can be increased when Nabumetone is combined with Sufentanil.
Methoxamine	The risk or severity of hypertension can be increased when Nabumetone is combined with Methoxamine.
Risperidone	The risk or severity of hypertension can be increased when Nabumetone is combined with Risperidone.
Isoflurane	The risk or severity of hypertension can be increased when Nabumetone is combined with Isoflurane.
Propiomazine	The risk or severity of hypertension can be increased when Nabumetone is combined with Propiomazine.
Alfentanil	The risk or severity of hypertension can be increased when Nabumetone is combined with Alfentanil.
Minaprine	The risk or severity of hypertension can be increased when Nabumetone is combined with Minaprine.
Orciprenaline	The risk or severity of hypertension can be increased when Nabumetone is combined with Orciprenaline.
Phenmetrazine	The risk or severity of hypertension can be increased when Nabumetone is combined with Phenmetrazine.
Pseudoephedrine	The risk or severity of hypertension can be increased when Nabumetone is combined with Pseudoephedrine.
Benzphetamine	The risk or severity of hypertension can be increased when Nabumetone is combined with Benzphetamine.
Ritodrine	The risk or severity of hypertension can be increased when Nabumetone is combined with Ritodrine.
Flupentixol	The risk or severity of hypertension can be increased when Nabumetone is combined with Flupentixol.
Remifentanil	The risk or severity of hypertension can be increased when Nabumetone is combined with Remifentanil.
Bitolterol	The risk or severity of hypertension can be increased when Nabumetone is combined with Bitolterol.
Oxymetazoline	The risk or severity of hypertension can be increased when Nabumetone is combined with Oxymetazoline.
Diethylpropion	The risk or severity of hypertension can be increased when Nabumetone is combined with Diethylpropion.
Salmeterol	The risk or severity of hypertension can be increased when Nabumetone is combined with Salmeterol.
Naratriptan	The risk or severity of hypertension can be increased when Nabumetone is combined with Naratriptan.
Formoterol	The risk or severity of hypertension can be increased when Nabumetone is combined with Formoterol.
Methoxyflurane	The risk or severity of hypertension can be increased when Nabumetone is combined with Methoxyflurane.
Ergoloid mesylate	The risk or severity of hypertension can be increased when Nabumetone is combined with Ergoloid mesylate.
Isoprenaline	The risk or severity of hypertension can be increased when Nabumetone is combined with Isoprenaline.
Arbutamine	The risk or severity of hypertension can be increased when Nabumetone is combined with Arbutamine.
Dutasteride	The risk or severity of hypertension can be increased when Nabumetone is combined with Dutasteride.
Halothane	The risk or severity of hypertension can be increased when Nabumetone is combined with Halothane.
Moclobemide	The risk or severity of hypertension can be increased when Nabumetone is combined with Moclobemide.
Pergolide	The risk or severity of hypertension can be increased when Nabumetone is combined with Pergolide.
Desflurane	The risk or severity of hypertension can be increased when Nabumetone is combined with Desflurane.
Bromocriptine	The risk or severity of hypertension can be increased when Nabumetone is combined with Bromocriptine.
Finasteride	The risk or severity of hypertension can be increased when Nabumetone is combined with Finasteride.
Aripiprazole	The risk or severity of hypertension can be increased when Nabumetone is combined with Aripiprazole.
Isocarboxazid	The risk or severity of hypertension can be increased when Nabumetone is combined with Isocarboxazid.
Ergometrine	The risk or severity of hypertension can be increased when Nabumetone is combined with Ergometrine.
Lisdexamfetamine	The risk or severity of hypertension can be increased when Nabumetone is combined with Lisdexamfetamine.
Fenoterol	The risk or severity of hypertension can be increased when Nabumetone is combined with Fenoterol.
Pirbuterol	The risk or severity of hypertension can be increased when Nabumetone is combined with Pirbuterol.
Ephedra sinica root	The risk or severity of hypertension can be increased when Nabumetone is combined with Ephedra sinica root.
Ephedrine	The risk or severity of hypertension can be increased when Nabumetone is combined with Ephedrine.
Mephentermine	The risk or severity of hypertension can be increased when Nabumetone is combined with Mephentermine.
Procaterol	The risk or severity of hypertension can be increased when Nabumetone is combined with Procaterol.
Yohimbine	The risk or severity of hypertension can be increased when Nabumetone is combined with Yohimbine.
Methotrimeprazine	The risk or severity of hypertension can be increased when Nabumetone is combined with Methotrimeprazine.
Clenbuterol	The risk or severity of hypertension can be increased when Nabumetone is combined with Clenbuterol.
Bambuterol	The risk or severity of hypertension can be increased when Nabumetone is combined with Bambuterol.
MMDA	The risk or severity of hypertension can be increased when Nabumetone is combined with MMDA.
Midomafetamine	The risk or severity of hypertension can be increased when Nabumetone is combined with Midomafetamine.
2,5-Dimethoxy-4-ethylamphetamine	The risk or severity of hypertension can be increased when Nabumetone is combined with 2,5-Dimethoxy-4-ethylamphetamine.
4-Methoxyamphetamine	The risk or severity of hypertension can be increased when Nabumetone is combined with 4-Methoxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamine	The risk or severity of hypertension can be increased when Nabumetone is combined with 4-Bromo-2,5-dimethoxyamphetamine.
Tenamfetamine	The risk or severity of hypertension can be increased when Nabumetone is combined with Tenamfetamine.
Chlorphentermine	The risk or severity of hypertension can be increased when Nabumetone is combined with Chlorphentermine.
Dextroamphetamine	The risk or severity of hypertension can be increased when Nabumetone is combined with Dextroamphetamine.
Phendimetrazine	The risk or severity of hypertension can be increased when Nabumetone is combined with Phendimetrazine.
Solifenacin	The risk or severity of hypertension can be increased when Nabumetone is combined with Solifenacin.
Periciazine	The risk or severity of hypertension can be increased when Nabumetone is combined with Periciazine.
Acepromazine	The risk or severity of hypertension can be increased when Nabumetone is combined with Acepromazine.
Thioproperazine	The risk or severity of hypertension can be increased when Nabumetone is combined with Thioproperazine.
Zuclopenthixol	The risk or severity of hypertension can be increased when Nabumetone is combined with Zuclopenthixol.
Epicaptopril	The risk or severity of hypertension can be increased when Nabumetone is combined with Epicaptopril.
Clorgiline	The risk or severity of hypertension can be increased when Nabumetone is combined with Clorgiline.
1-benzylimidazole	The risk or severity of hypertension can be increased when Nabumetone is combined with 1-benzylimidazole.
Nialamide	The risk or severity of hypertension can be increased when Nabumetone is combined with Nialamide.
Lysergic acid diethylamide	The risk or severity of hypertension can be increased when Nabumetone is combined with Lysergic acid diethylamide.
Dronedarone	The risk or severity of hypertension can be increased when Nabumetone is combined with Dronedarone.
Flibanserin	The risk or severity of hypertension can be increased when Nabumetone is combined with Flibanserin.
Iloperidone	The risk or severity of hypertension can be increased when Nabumetone is combined with Iloperidone.
Indacaterol	The risk or severity of hypertension can be increased when Nabumetone is combined with Indacaterol.
Rotigotine	The risk or severity of hypertension can be increased when Nabumetone is combined with Rotigotine.
Amibegron	The risk or severity of hypertension can be increased when Nabumetone is combined with Amibegron.
Naluzotan	The risk or severity of hypertension can be increased when Nabumetone is combined with Naluzotan.
Cariprazine	The risk or severity of hypertension can be increased when Nabumetone is combined with Cariprazine.
Pizotifen	The risk or severity of hypertension can be increased when Nabumetone is combined with Pizotifen.
Solabegron	The risk or severity of hypertension can be increased when Nabumetone is combined with Solabegron.
Esmirtazapine	The risk or severity of hypertension can be increased when Nabumetone is combined with Esmirtazapine.
Vilazodone	The risk or severity of hypertension can be increased when Nabumetone is combined with Vilazodone.

Target Protein

Prostaglandin G/H synthase 2 PTGS2

Prostaglandin G/H synthase 1 PTGS1

Referensi & Sumber

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

Artikel (PubMed)

PMID: 9435990
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.
PMID: 24659525
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.
PMID: 23584048
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.
PMID: 19204080
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.
PMID: 24083957
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.
PMID: 22981510
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.
PMID: 23063076
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.
PMID: 1474529
Blower PR: The unique pharmacologic profile of nabumetone. J Rheumatol Suppl. 1992 Nov;36:13-9.

Textbook

ISBN: 978-1-25-958473-2
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.

Link

Contoh Produk & Brand

Produk: 212 • International brands: 9

Produk

Mylan-nabumetone

Tablet • 500 mg • Oral • Canada • Generic • Approved
Nabumetone

Tablet • 750 mg/1 • Oral • US • Generic • Approved
Nabumetone

Tablet, film coated • 750 mg/1 • Oral • US • Generic • Approved
Nabumetone

Tablet • 500 mg/1 • Oral • US • Generic • Approved
Nabumetone

Tablet • 750 mg/1 • Oral • US • Generic • Approved
Nabumetone

Tablet • 500 mg/1 • Oral • US • Generic • Approved
Nabumetone

Tablet, film coated • 500 mg/1 • Oral • US • Generic • Approved
Nabumetone

Tablet, film coated • 750 mg/1 • Oral • US • Generic • Approved

Menampilkan 8 dari 212 produk.

International 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)

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.