Nabumetone

Nabumetone
Systematic (IUPAC) name
4-(6-methoxy-2-naphthyl)-2-butanone
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a692022
  • AU: Prescription Only (S4)
  • POM
Oral
Pharmacokinetic data
Protein binding > 99% (active metabolite)
Metabolism Hepatic, to active metabolite 6-methoxy-2-naphthylacetic acid; 6-MNA
Half-life 23 hours (active metabolite)
Excretion Renal
Identifiers
42924-53-8 Yes
M01AX01
PubChem CID 4409
DrugBank DB00461 Yes
ChemSpider 4256 Yes
UNII LW0TIW155Z Yes
KEGG D00425 Yes
ChEBI CHEBI:7443 
ChEMBL CHEMBL1070 Yes
Chemical data
Formula C15H16O2
228.29 g/mol
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Nabumetone is a non-steroidal anti-inflammatory drug[1] (NSAID), the only 1-naphthaleneacetic acid derivative. Nabumetone has been developed by Beecham. It is available under numerous brand names, such as Relafen, Relifex, and Gambaran.

Introduction

Nabumetone is a non acidic NSAID that is rapidly metabolized in the liver to a major 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.[2]

Nabumetone belongs to a new class of NSAID with a lower potential for causing gastrointestinal mucosal irritancy and inhibition of platelet function,[3] little effect on renal prostaglandin secretion and less of an association with heart failure than other traditional drugs of the class.[4] Effects of nabumetone on blood pressure control in hypertensive patients on ACE inhibitors is also good—equivalent to Paracetamol.[5]

Uses

It is used to treat pain or inflammation caused by arthritis or other inflammatory diseases and conditions like synovitis. Nabumetone works by reducing the effects of enzymes that cause pain and inflammation.

Side effects

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.

Assay of nabumetone

There are few papers published reporting analytical methods[6] for nabumetone.[7] Two of them employed HPLC with UV-detection.[8][9] One HPLC method using direct injection on restricted access media columns.[10] Flow injection analysis (FIA) with UV-detection was also reported for the determination of nabumetone in pharmaceutical preparations.[11] Methods using HPLC with fluorescence detection [12][13][14][15] 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,[7] photodiode array (PDA) detector[16][17] and mass spectrometric detection for the determination of nabumetone and its metabolites. Murillo Pulgarín et al.[18][19][20] reported three analytical methods using different techniques along with phosphorescence. Liquid chromatography methods using different techniques of mass spectrometry were also reported.[21][22][23] The electrochemical behavior of nabumetone by a voltammetric technique [24] and a novel colorimetric method based on chemical derivatization [25] were also published. P. K. Sahu et al.[26] has reported a HPLC method for simultaneous estimation of Nabumetone and Paracetamol in combined dosage form.

References

  1. ↑ 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 : official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 17 (4): 274–6. PMID 17694703.
  2. ↑ Olsen N V, Jensen N G, Hansen J M, Christensen N J, Fogh-Andersen N and Kanstrup I L, Clin Sci.,1999, 97, 457- 465.
  3. ↑ Kristensen Jrgen, Viklund Andreas, Feltelius Nils and Larsson Anders, Platelets. 1996, 7, 149 - 152.
  4. ↑ Donnan P T, Pharmacoepidemiol Drug Safety, 2000, 8, 115.
  5. ↑ Palmer Robert H, Haig Ann E, Flavin Susan K and Iyengar Malini K, Am J Hypertens. 2001, 14, 85A.
  6. ↑ Małgorzata, Starek; Jan, Krzek (2009). Talanta 77: 925–942. Missing or empty |title= (help)
  7. ↑ 7.0 7.1 Sahu, Prafulla Kumar; Annapurna, M. Mathrusri (2009). "Analysis of Nabumetone in Bulk and Tablet Formulation by a New and Validated Reverse Phase High Performance Liquid Chromatography". E-Journal of Chemistry. 6(S1): S59–S64. ISSN 0973-4945.
  8. ↑ Al-Momani Idrees F, Anal Lett., 1997, 30, 2485-2492.
  9. ↑ Jang E J, Lee Y J, Park M G and Shim C K, Anal Lett., 1995, 28, 2379-2389.
  10. ↑ Haque Ahsanul and Stewart James T, Biomed Chromatogr., 1999, 13, 51-56.
  11. ↑ Can N O, Tuncel M and Aboul-Enein H Y, Pharmazie., 2003, 58, 22-24.
  12. ↑ Mikami E, Goto T, Ohno T, Matsumoto H and Nishida M, J Pharm Biomed Anal., 2000, 23, 917-925.
  13. ↑ ska Kamila Kobyli, Ska Ma gorzata Barli and Ska Maria Kobyli, J Pharm Biomed Anal., 2003, 32, 323-328.
  14. ↑ Nobilis M, Kopecký J, Tina J Kv, Svoboda Z, Pour M, Kune J, Apek M Hol and Ová L Kolá, J Pharm Biomed Anal., 2003, 32, 641-656.
  15. ↑ Al-Rawashdeh A F Nathir, J Inclusion Phenomena and Macrocyclic Chem. 2005, 51(1-2), 27-32.
  16. ↑ Rao R Nageswara, Meena S, Nagaraju D and Rao A Raghu Ram, Biomed Chromatogr., 2004, 19, 362-368.
  17. ↑ Nobilis M, Holcapek M, Kolárová L, Kopecký J, Kunes M, Svoboda Z and Kvetina J, J Chromatogr. A, 2004, 1031, 229-236.
  18. ↑ Pulgarín J A Murillo, Molina A Alañón and Pardo M T Alañón, Analytica Chimica Acta, 2005, 528, 77-82.
  19. ↑ Pulgarín J A Murillo, Molina A Alañón and Pardo M T Alañón, Anal Biochem., 2005, 339, 157-164.
  20. ↑ Pulgarín Jose A Murillo, Molina Aurelia Alañón and Robles Ignacio Sánchez-Ferrer, Analytica Chimica Acta. 2005, 554, 37-42.
  21. ↑ Patel Bhavin N, Sharma Naveen, Sanyal Mallika, Prasad Arpana and Shrivastav Pranav S, Biomed Chromatogr., 2008, 22, 1213-1224.
  22. ↑ Wolff J C, Hawtin P N, Monté S, Balogh M and Jones T, Rapid Commun Mass Spectrom., 2001, 15, 265-272.
  23. ↑ Sheen, J F; Her, G R (December 2004). "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". Anal Bioanal Chem 380 (7–8): 891–7. doi:10.1007/s00216-004-2877-6.
  24. ↑ Altun Yuksel, Dogan Burcu, Ozkan Sibel A and Uslu Bengi, Acta Chim Slov., 2007, 54, 287-294.
  25. ↑ Adegoke A O, Idowu S O and Olaniyi A A, Afr J Med Med Sci., 2007, 36, 249-257.
  26. ↑ Sahu, Prafulla Kumar; Annapurna, M. Mathrusri; Sahoo, Dillip Kumar (2011). "A Simple and Sensitive HPLC Method for Simultaneous Analysis of Nabumetone and Paracetamol in Pharmaceutical Formulations". E-Journal of Chemistry 8 (S1): S41–S46. doi:10.1155/2011/607069.