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Clinical data
Routes of
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
Pharmacokinetic data
Protein binding> 99% (active metabolite)
MetabolismHepatic, to active metabolite 6-methoxy-2-naphthylacetic acid; 6-MNA
Elimination half-life23 hours (active metabolite)
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.169.752 Edit this at Wikidata
Chemical and physical data
Molar mass228.291 g·mol−1
3D model (JSmol)
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Three step CYP1A2 Mediated Metabolism of the prodrug Nabumetone to its active metabolite 6-MNA.[1]

Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID).[2] Nabumetone has been developed by Beecham. It is available under numerous brand names, such as Relafen, Relifex, and Gambaran.

Nabumetone is a nonacidic NSAID prodrug that is rapidly metabolized in the liver to the active metabolite, 6-methoxy-2-naphthyl acetic acid. As found with previous NSAIDs, nabumetone's active metabolite inhibits the cyclooxygenase enzyme and preferentially blocks COX-2 activity (which is indirectly responsible for the production of inflammation and pain during arthritis). The active metabolite of nabumetone is felt to be the compound primarily responsible for therapeutic effect. Comparatively, the parent drug is a poor inhibitor of COX-2 byproducts, particularly prostaglandins. It may be less nephrotoxic than indomethacin.[3] There are two known polymorphs of the compound.[4]

Nabumetone has little effect on renal prostaglandin secretion and less of an association with heart failure than other traditional drugs of the class.[5] Effects of nabumetone on blood pressure control in hypertensive patients on ACE inhibitors is also good—equivalent to paracetamol.[6] As of 2015 the cost for a typical month of medication in the United States is 25 to US$50.[7]

Medical uses[edit]

Similar in action to other NSAIDs, Nabumetone is used to treat pain and inflammation.[citation needed]

Side effects[edit]

It has been shown to have a slightly lower risk of gastrointestinal side effects than most other non-selective NSAIDs since it is a non-acidic prodrug which is then metabolized to its active 6MNA (6-methoxy-2-naphthylacetic acid) form.[citation needed]

Side effects include: Bloody or black, tarry stools; change in color, frequency, or amount of urine; chest pain; shortness of breath; coughing up blood; pale stools; numbness; weakness; flu-like symptoms; leg pain; vision problems; speech problems; problems walking; weight gain; stomach pain; cold sweat; skin rash; blisters; headache; swelling; bleeding; bruising; vomiting blood; jaundice; diarrhea; constipation; dizziness; indigestion; gas; nausea; and ringing in the ears.[8]

In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.[9][10] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.[9][10]

Assay of nabumetone[edit]

There are few papers published reporting analytical methods[11] for nabumetone.[12] Two of them employed HPLC with UV-detection.[13][14] One HPLC method using direct injection on restricted access media columns.[15] Flow injection analysis (FIA) with UV-detection was also reported for the determination of nabumetone in pharmaceutical preparations.[16] Methods using HPLC with fluorescence detection [17][18][19][20] were reported. M. Nobilis et al. carried out biotransformation and disposition studies in humans and minipigs using HPLC with UV, fluorescence and mass spectrometric detection. The interactions with gamma-cyclodextrin were also studied by fluorescence measurements. Assay methods employed HPLC using UV detection,[12] photodiode array (PDA) detector[21][22] and mass spectrometric detection for the determination of nabumetone and its metabolites. Murillo Pulgarín et al.[23][24][25] reported three analytical methods using different techniques along with phosphorescence. Liquid chromatography methods using different techniques of mass spectrometry were also reported.[26][27][28] The electrochemical behavior of nabumetone by a voltammetric technique [29] and a novel colorimetric method based on chemical derivatization [30] were also published. P. K. Sahu et al.[31] has reported a HPLC method for simultaneous estimation of nabumetone and paracetamol in combined dosage form.


  1. ^ Varfaj, F.; Zulkifli, S. N. A.; Park, H.-G.; Challinor, V. L.; De Voss, J. J.; Ortiz de Montellano, P. R. (2014-02-28). "Carbon-Carbon Bond Cleavage in Activation of the Prodrug Nabumetone". Drug Metabolism and Disposition. 42 (5): 828–838. doi:10.1124/dmd.114.056903. ISSN 1521-009X. PMC 3989788. PMID 24584631.
  2. ^ Gonzalo-Garijo MA, Cordobés-Duran C, Lamilla-Yerga AM, Moreno-Gastón I (2007). "Severe immediate reaction to nabumetone". Journal of Investigational Allergology and Clinical Immunology. 17 (4): 274–6. PMID 17694703.
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  4. ^ Price, C P; Grzesiak, A L; Lang, M; Matzger, A J (2002). "Polymorphism of Nabumetone". Crystal Growth & Design. 2 (6): 501–503. doi:10.1021/cg0255568.
  5. ^ Donnan, P T (2000). "098. A Drug-Safety Study to Examine the Possible Association of Congestive Heart Failure with Dispensed Nabumetone, Ibuprofen and other Non-Steroidal Anti-inflammatory Drugs". Pharmacoepidemiology & Drug Safety. 8 (S2): S115. doi:10.1002/(SICI)1099-1557(199908)8:2+<S79::AID-PDS429>3.0.CO;2-2.
  6. ^ Palmer, Robert H; Haig, Ann E; Flavin, Susan K; Iyengar, Malini K (2001). "Effects of ibuprofen (IB), nabumetone (N) and celecoxib (C) on blood pressure (BP) control in hypertensive patients on ACE inhibitors". American Journal of Hypertension. 14 (S1): 85A. doi:10.1016/S0895-7061(01)01811-8.
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  8. ^ "Relafen (Nabumetone): Side Effects, Interactions, Warning, Dosage & Uses". RxList. Retrieved 2018-03-09.
  9. ^ a b "FDA Warns that Using a Type of Pain and Fever Medication in Second Half of Pregnancy Could Lead to Complications". U.S. Food and Drug Administration (FDA) (Press release). 15 October 2020. Retrieved 15 October 2020. This article incorporates text from this source, which is in the public domain.
  10. ^ a b "NSAIDs may cause rare kidney problems in unborn babies". U.S. Food and Drug Administration. 21 July 2017. Retrieved 15 October 2020. This article incorporates text from this source, which is in the public domain.
  11. ^ Małgorzata, Starek; Jan, Krzek (2009). "A review of analytical techniques for determination of oxicams, nimesulide and nabumetone". Talanta. 77 (3): 925–942. doi:10.1016/j.talanta.2008.09.022. PMID 19064072.
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  14. ^ Jang, E J; Lee, Y J; Park, M G; Shim, C K (1995). "HPLC Assay of 6-Methoxy-2-Naphthylacetic Acid, a Major Metabolite of Nabumetone, in Human Serum". Analytical Letters. 28 (13): 2379–2389. doi:10.1080/00032719508000379.
  15. ^ Ahsanul, Haque; Stewart James, T (1999). "Direct injection hplc analysis of some non‐steroidal anti‐inflammatory drugs on restricted access media columns". Biomedical Chromatography. 13 (1): 51–56. doi:10.1002/(sici)1099-0801(199902)13:1<51::aid-bmc814>;2-k. PMID 10191944.
  16. ^ Can, N O; Tuncel, M; Aboul-Enein, H Y (2003). "Determination of nabumetone in pharmaceutical formulation by flow injection analysis (FIA) with UV-detection". Die Pharmazie. 58 (1): 22–24. PMID 12622247.
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  18. ^ Kobylińska, Kamila; Barlińska, Małgorzata; Kobylińska, Maria (2003). "Analysis of nabumetone in human plasma by HPLC. Application to single dose pharmacokinetic studies". Journal of Pharmaceutical and Biomedical Analysis. 2003 (32): 323–328. doi:10.1016/S0731-7085(03)00078-5. PMID 12763542.
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  20. ^ Al-Rawashdeh, A F Nathir (2005). "Interactions of Nabumetone with γ-Cyclodextrin Studied by Fluorescence Measurements". Journal of Inclusion Phenomena and Macrocyclic Chemistry. 51 (1–2): 27–32. doi:10.1007/s10847-004-1502-9. S2CID 96877641.
  21. ^ Nageswara, Rao R; Meena, S; Nagaraju, D; Raghu Ram, Rao A (2004). "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". Biomedical Chromatography. 19 (5): 362–368. doi:10.1002/bmc.458. PMID 15627281.
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  26. ^ Patel Bhavin, N; Naveen, Sharma; Mallika, Sanyal; Arpana, Prasad; Shrivastav Pranav, S (2008). "High-throughput LC-MS/MS assay for 6-methoxy-2-naphthylacetic acid, an active metabolite of nabumetone in human plasma and its application to bioequivalence study". Biomedical Chromatography. 22 (11): 1213–1224. doi:10.1002/bmc.1047. PMID 18651608.
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