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Pathway Description
Ibuprofen Metabolism Pathway
Homo sapiens
Drug Metabolism Pathway
Created: 2013-09-11
Last Updated: 2019-10-29
Ibuprofen is a very common NSAID drug used to treat pain and inflammation. This includes headaches, muscle pain and fever. It is sold under the brand name Advil or Motrin. Ibuprofen is typically ingested orally, although in the USA an intravenous version can be used. It inhibits cyclooxygenase (COX) non-selectively. This enzyme is responsible for the creation of prostaglandins, which allow pain to be felt. Inhibiting COX makes prostaglandin creation more sparse, thus resulting in less pain for the patient using ibuprofen. Arachdonic acid is converted into prostaglandin H2 by using cytosolic prostaglandin G/H synthase (COX). These enzymes are available as COX1 and COX2, and are encoded by PTGS1 (COX1) and PTGS2 (COX2). Ibuprofen may also inhibit fatty acid amide hydrolase (FAAH), which results in the activation of antinociceptive axis, which then metabolizes the endocannabinoid anandamide.
References
Ibuprofen Pathway References
Advil. (2009). e-CPS (online version of Compendium of Pharmaceuticals and Specialties). Retrieved August 15, 2009.
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Pubmed: 10049739
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Pubmed: 14702039
Hsieh KP, Lin YY, Cheng CL, Lai ML, Lin MS, Siest JP, Huang JD: Novel mutations of CYP3A4 in Chinese. Drug Metab Dispos. 2001 Mar;29(3):268-73.
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Molowa DT, Schuetz EG, Wrighton SA, Watkins PB, Kremers P, Mendez-Picon G, Parker GA, Guzelian PS: Complete cDNA sequence of a cytochrome P-450 inducible by glucocorticoids in human liver. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5311-5. doi: 10.1073/pnas.83.14.5311.
Pubmed: 3460094
Gonzalez FJ, Schmid BJ, Umeno M, Mcbride OW, Hardwick JP, Meyer UA, Gelboin HV, Idle JR: Human P450PCN1: sequence, chromosome localization, and direct evidence through cDNA expression that P450PCN1 is nifedipine oxidase. DNA. 1988 Mar;7(2):79-86. doi: 10.1089/dna.1988.7.79.
Pubmed: 3267210
Dai D, Zeldin DC, Blaisdell JA, Chanas B, Coulter SJ, Ghanayem BI, Goldstein JA: Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid. Pharmacogenetics. 2001 Oct;11(7):597-607.
Pubmed: 11668219
Okino ST, Quattrochi LC, Pendurthi UR, McBride OW, Tukey RH: Characterization of multiple human cytochrome P-450 1 cDNAs. The chromosomal localization of the gene and evidence for alternate RNA splicing. J Biol Chem. 1987 Nov 25;262(33):16072-9.
Pubmed: 3500169
Kimura S, Pastewka J, Gelboin HV, Gonzalez FJ: cDNA and amino acid sequences of two members of the human P450IIC gene subfamily. Nucleic Acids Res. 1987 Dec 10;15(23):10053-4. doi: 10.1093/nar/15.23.10053.
Pubmed: 3697070
Miyazawa M, Shindo M, Shimada T: Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metab Dispos. 2002 May;30(5):602-7. doi: 10.1124/dmd.30.5.602.
Pubmed: 11950794
Ibeanu GC, Goldstein JA, Meyer U, Benhamou S, Bouchardy C, Dayer P, Ghanayem BI, Blaisdell J: Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. J Pharmacol Exp Ther. 1998 Sep;286(3):1490-5.
Pubmed: 9732415
Ibeanu GC, Blaisdell J, Ghanayem BI, Beyeler C, Benhamou S, Bouchardy C, Wilkinson GR, Dayer P, Daly AK, Goldstein JA: An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians. Pharmacogenetics. 1998 Apr;8(2):129-35.
Pubmed: 10022751
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Pubmed: 2827463
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