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Pathway Description
Nabumetone Action Pathway
Homo sapiens
Drug Action Pathway
Nabumetone (also named Relafen and Relifex) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to relieve pain (analgesic) and reduce fever (antipyretic). Nabumetone can block prostaglandin synthesis by the action of inhibition of prostaglandin G/H synthase 1 and 2. Prostaglandin G/H synthase 1 and 2 catalyze the arachidonic acid to prostaglandin G2, and also catalyze prostaglandin G2 to prostaglandin H2 in the metabolism pathway. Since prostaglandin is the messenger molecules in the process of inflammation; hence, inhibition of prostaglandin synthesis can reduce the pain, fever and inflammation.
References
Nabumetone Pathway References
Botting, R., & Botting, J. Cyclooxygenases. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology. (2004) p.279-283. Berlin, Germany: Springer.
Breyer, R.M., & Breyer, M.D. Prostanoids. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology. (2004) p. 752-757. Berlin, Germany: Springer.
Lister BJ, Poland M, DeLapp RE: Efficacy of nabumetone versus diclofenac, naproxen, ibuprofen, and piroxicam in osteoarthritis and rheumatoid arthritis. Am J Med. 1993 Aug 9;95(2A):2S-9S. doi: 10.1016/0002-9343(93)90390-b.
Pubmed: 8356999
Patel BN, Sharma N, Sanyal M, Prasad A, Shrivastav PS: 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. 2008 Nov;22(11):1213-24. doi: 10.1002/bmc.1047.
Pubmed: 18651608
Boyle EA, Freeman PC, Mangan FR, Thomson MJ: Nabumetone (BRL 14777, 4-[6-methoxy-2-naphthyl]-butan-2-one): a new anti-inflammatory agent. J Pharm Pharmacol. 1982 Sep;34(9):562-9. doi: 10.1111/j.2042-7158.1982.tb04794.x.
Pubmed: 6127380
Makarowski W, Weaver A, Rubin B, Caldwell J, McMahon FG, Noveck RJ, Lee D, Offenberg H, Sack M, Sikes D, Trapp R, Rush S, Kuss M, Ganju J, Bocanegra TS, Ratliff JM: The efficacy, tolerability, and safety of 1200 mg/d of oxaprozin and 1500 mg/d of nabumetone in the treatment of patients with osteoarthritis of the knee. Clin Ther. 1996 Jan-Feb;18(1):114-24.
Pubmed: 8851458
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. doi: 10.2165/00003495-200464200-00004.
Pubmed: 15456329
Rothstein R: Safety profiles of leading nonsteroidal anti-inflammatory drugs. Am J Med. 1998 Nov 2;105(5A):39S-43S. doi: 10.1016/s0002-9343(98)00280-0.
Pubmed: 9855175
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
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
Arachidonic Acid Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Kroetz DL, Zeldin DC: Cytochrome P450 pathways of arachidonic acid metabolism. Curr Opin Lipidol. 2002 Jun;13(3):273-83.
Pubmed: 12045397
Zeldin DC: Epoxygenase pathways of arachidonic acid metabolism. J Biol Chem. 2001 Sep 28;276(39):36059-62. doi: 10.1074/jbc.R100030200. Epub 2001 Jul 12.
Pubmed: 11451964
Ondrey FG: Arachidonic acid metabolism: a primer for head and neck surgeons. Head Neck. 1998 Jul;20(4):334-49.
Pubmed: 9588707
Sigal E: The molecular biology of mammalian arachidonic acid metabolism. Am J Physiol. 1991 Feb;260(2 Pt 1):L13-28. doi: 10.1152/ajplung.1991.260.2.L13.
Pubmed: 1899973
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