Nabumetone

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Nabumetone
Clinical data
AHFS/Drugs.com Monograph
MedlinePlus a692022
Routes of
administration		 Oral
ATC code M01AX01 (WHO)
Legal status
Legal status
  • AU: S4 (Prescription only)
  • POM
Pharmacokinetic data
Protein binding > 99% (active metabolite)
Metabolism Hepatic, to active metabolite 6-methoxy-2-naphthylacetic acid; 6-MNA
Biological half-life 23 hours (active metabolite)
Excretion Renal
Identifiers
CAS Number 42924-53-8 YesY
PubChem (CID) 4409
IUPHAR/BPS 7245
DrugBank DB00461 YesY
ChemSpider 4256 YesY
UNII LW0TIW155Z YesY
KEGG D00425 YesY
ChEBI CHEBI:7443 N
ChEMBL CHEMBL1070 YesY
ECHA InfoCard 100.169.752
Chemical and physical data
Formula C15H16O2
Molar mass 228.29 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

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.

Nabumetone is a nonacidic 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 has little effect on renal prostaglandin secretion and less of an association with heart failure than other traditional drugs of the class.[3] Effects of nabumetone on blood pressure control in hypertensive patients on ACE inhibitors is also good—equivalent to paracetamol.[4] As of 2015 the cost for a typical month of medication in the United States is 25 to 50 USD.[5]

Medical uses

It is 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. 17 (4): 274–6. PMID 17694703.
  2. ↑ Olsen, N V; Jensen, N G; Hansen, J M; Christensen, N J; Fogh-Andersen, N; Kanstrup, I L (1999). "Non-steroidal anti-inflammatory drugs and renal response to exercise: a comparison of indomethacin and nabumetone". Clin Sci. 97: 457–465. doi:10.1042/cs0970457.
  3. ↑ 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". Pharmacoepidemiol Drug Safety. 8 (S2): S115. doi:10.1002/(SICI)1099-1557(199908)8:2+<S79::AID-PDS429>3.0.CO;2-2.
  4. ↑ Palmer Robert, H; Haig Ann, E; Flavin Susan, K; Iyengar Malini, K (2001). Am J Hypertens. 14 (S1): 85A. Missing or empty |title= (help)
  5. ↑ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 9. ISBN 9781284057560.
  6. ↑ Małgorzata, Starek; Jan, Krzek (2009). "A review of analytical techniques for determination of oxicams, nimesulide and nabumetone". Talanta. 77: 925–942. doi:10.1016/j.talanta.2008.09.022.
  7. 1 2 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. "Determination of Nabumetone and Its Major Metabolite in Plasma and Tablet Formulations by Reverse-Phase HPLC". Anal Lett. 1997 (30): 2485–2492. doi:10.1080/00032719708001759.
  9. ↑ 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". Anal Lett. 28: 2379–2389. doi:10.1080/00032719508000379.
  10. ↑ Ahsanul, Haque; Stewart James, T (1999). "Direct injection hplc analysis of some non‐steroidal anti‐inflammatory drugs on restricted access media columns". Biomed Chromatogr. 13: 51–56. doi:10.1002/(sici)1099-0801(199902)13:1<51::aid-bmc814>3.3.co;2-k.
  11. ↑ Can, N O; Tuncel, M; Aboul-Enein, H Y (2003). "Determination of nabumetone in pharmaceutical formulation by flow injection analysis (FIA) with UV-detection.". Pharmazie. 58: 22–24. PMID 12622247.
  12. ↑ Mikami, E; Goto, T; Ohno, T; Matsumoto, H; Nishida, M (2000). "Simultaneous analysis of naproxen, nabumetone and its major metabolite 6-methoxy-2-naphthylacetic acid in pharmaceuticals and human urine by high-performance liquid chromatography". J Pharm Biomed Anal. 23: 917–925. doi:10.1016/s0731-7085(00)00365-4.
  13. ↑ Kobylińska, Kamila; Barlińska, Małgorzata; Kobylińska, Maria. "Analysis of nabumetone in human plasma by HPLC. Application to single dose pharmacokinetic studies". J Pharm Biomed Anal. 2003 (32): 323–328. doi:10.1016/S0731-7085(03)00078-5.
  14. ↑ Nobilis, M; Kopecký, J; Kv, Tina J; Svoboda, Z; Pour, M; Kune, J; Hol, Apek M; Kolá, Ová L (2003). "Comparative biotransformation and disposition studies of nabumetone in humans and minipigs using high-performance liquid chromatography with ultraviolet, fluorescence and mass spectrometric detection". J Pharm Biomed Anal. 32: 641–656. doi:10.1016/s0731-7085(03)00171-7.
  15. ↑ Al-Rawashdeh, A F Nathir (2005). "Interactions of Nabumetone with γ-Cyclodextrin Studied by Fluorescence Measurements". J Inclusion Phenomena and Macrocyclic Chem. 51 (1-2): 27–32. doi:10.1007/s10847-004-1502-9.
  16. ↑ 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". Biomed Chromatogr. 19: 362–368. doi:10.1002/bmc.458.
  17. ↑ Nobilis, M; Holcapek, M; Kolárová, L; Kopecký, J; Kunes, M; Svoboda, Z; Kvetina, J (2004). "Identification and determination of phase II nabumetone metabolites by high-performance liquid chromatography with photodiode array and mass spectrometric detection". J Chromatogr. A. 1031: 229–236. doi:10.1016/j.chroma.2004.01.031.
  18. ↑ Murillo, Pulgarín J A; Alañón, Molina A; Alañón, Pardo M T (2005). "Simplex optimization and kinetic determination of nabumetone in pharmaceutical preparations by micellar—stabilized room temperature phosphorescence". Analytica Chimica Acta. 528: 77–82. doi:10.1016/j.aca.2004.10.014.
  19. ↑ Murillo, Pulgarín J A; Alañón, Molina A; Alañón, Pardo M T (2005). "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". Anal Biochem. 339: 157–164. doi:10.1016/j.ab.2005.01.012.
  20. ↑ Pulgarín; Murillo, Jose A; Aurelia Alañón, Molina; Robles Ignacio, Sánchez-Ferrer (2005). "Simple and rapid determination of the active metabolite of nabumetone in biological fluids by heavy atom-induced room temperature phosphorescence". Analytica Chimica Acta. 554: 37–42. doi:10.1016/j.aca.2005.08.040.
  21. ↑ 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". Biomed Chromatogr. 22: 1213–1224. doi:10.1002/bmc.1047.
  22. ↑ Wolff, J C; Hawtin, P N; Monté, S; Balogh, M; Jones, T (2001). "The use of particle beam mass spectrometry for the measurement of impurities in a nabumetone drug substance, not easily amenable to atmospheric pressure ionisation techniques". Rapid Commun Mass Spectrom. 15: 265–272. doi:10.1002/rcm.214.
  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. ↑ Yuksel, Altun; Burcu, Dogan; Ozkan Sibel, A; Bengi, Uslu (2007). "Development and Validation of Voltammetric Techniques for Nabumetone in Pharmaceutical Dosage Form, Human Serum and Urine". Acta Chim Slov. 54: 287–294.
  25. ↑ Adegoke, A O; Idowu, S O; Olaniyi, A A (2007). "Novel determination of nabumetone, a cox-2 inhibitor precursor via its 4-carboxyl-2,6-dinitrobenzene diazonium (CDNBD) derived AZO dye.". Afr J Med Med Sci. 36: 249–257. PMID 18390065.
  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" (PDF). E-Journal of Chemistry. 8 (S1): S41–S46. doi:10.1155/2011/607069.
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