Uneingeschränkter Zugang

How polymorphisms of the cytochrome P450 genes affect ibuprofen and diclofenac metabolism and toxicity / Kako polimorfizmi gena citokroma P450 utječu na metabolizam i toksičnost ibuprofena i diklofenaka


1. Ma Q, Lu AY. Pharmacogenetics, pharmacogenomics, and individualized medicine. Pharmacol Rev 2011;63:437-59. doi: 10.1124/pr.110.00353310.1124/pr.110.00353321436344Search in Google Scholar

2. Božina N, Bradamante V, Lovrić M. Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh Hig Rada Toksikol 2009;60:217-42. doi: 10.2478/10004-1254-60-2009-188510.2478/10004-1254-60-2009-188519581216Search in Google Scholar

3. Swen JJ, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee AH, Mulder H, Rongen GA, van Schaik RH, Schalekamp T, Touw DJ, van der Weide J, Wilffert B, Deneer VH, Guchelaar HJ. Pharmacogenetics: from bench to byte--an update of guidelines. Clin Pharmacol Ther 2011;89:662-73. doi: 10.1038/clpt.2011.3410.1038/clpt.2011.3421412232Search in Google Scholar

4. Warner TD, Giuliano F, Vojnovic I, Bukasa A, Mitchell JA, Vane JR. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci USA 1999;96:7563-8. PMID: 1037745510.1073/pnas.96.13.75632212610377455Search in Google Scholar

5. Bleumink GS, Feenstra J, Sturkenboom MC, Stricker BH. Nonsteroidal antiinflammatory drugs and heart failure. Drugs 2003;63:525-34. PMID: 1265665110.2165/00003495-200363060-0000112656651Search in Google Scholar

6. Jinno N, Tagashira M, Tsurui K, Yamada S. Contribution of cytochrome P450 and UDP-glucuronosyltransferase to the metabolism of drugs containing carboxylic acid groups: risk assessment of acylglucuronides using human hepatocytes. Xenobiotica 2014;44:677-86. doi: 10.3109/00498254.2014. 894219Search in Google Scholar

7. Zhang Y, Han YH, Putluru SP, Matta MK, Kole P, Mandlekar S, Furlong MT, Liu T, Iyer RA, Marathe P, Yang Z, Lai Y, Rodrigues AD. Diclofenac and its acyl glucuronide: determination of in vivo exposure in human subjects and characterization as human drug transporter substrates in vitro. Drug Metab Dispos 2016;44:320-8. doi: 10.1124/ dmd.115.06694410.1124/dmd.115.06694426714763Search in Google Scholar

8. Kindla J, Müller F, Mieth M, Fromm MF, König J. Influence of non-steroidal anti-inflammatory drugs on organic anion transporting polypeptide (OATP) 1B1- and OATP1B3- mediated drug transport. Drug Metab Dispos 2011;39:1047-53. doi: 10.1124/dmd.110.03762210.1124/dmd.110.03762221389119Search in Google Scholar

9. Rudy AC, Knight PM, Brater DC, Hall SD. Stereoselective metabolism of ibuprofen in humans: administration of R-, S- and racemic ibuprofen. J Pharmacol Exp Ther 1991;259:1133-9. PMID: 1762067Search in Google Scholar

10. Woodman TJ, Wood PJ, Thompson AS, Hutchings TJ, Steel GR, Jiao P, Threadgill MD, Lloyd MD. Chiral inversion of 2-arylpropionyl-CoA esters by human α-methylacyl-CoA racemase 1A (P504S): a potential mechanism for the anticancer effects of ibuprofen. Chem Commun (Camb) 2011;47:7332-4. doi: 10.1039/c1cc10763a10.1039/c1cc10763a21614403Search in Google Scholar

11. Davies NM. Clinical pharmacokinetics of ibuprofen. The first 30 years. Clin Pharmacokinet 1998;34:101-54. doi: 10.2165/00003088-199834020-0000210.2165/00003088-199834020-000029515184Search in Google Scholar

12. Neunzig I, Göhring A, Drăgan CA, Zapp J, Peters FT, Maurer HH, Bureik M.. Production and NMR analysis of the human ibuprofen metabolite 3-hydroxyibuprofen. J Biotechnol 2012;157:417-20. doi: 10.1016/j.jbiotec.2011.12.01610.1016/j.jbiotec.2011.12.01622226725Search in Google Scholar

13. Hamman MA, Thompson GA, Hall SD. Regioselective and stereoselective metabolism of ibuprofen by human Cytochrome P450 2C. Biochem Pharmacol 1997;54:33-41. doi: 10.1016/ S0006-2952(97)00143-310.1016/S0006-2952(97)00143-3Search in Google Scholar

14. Chang SY, Li W, Traeger SC, Wang B, Cui D, Zhang H, Wen B, Rodrigues AD. Confirmation that Cytochrome P450 2C8 (CYP2C8) plays a minor role in (S)-(+)- and (R)-(-)-ibuprofen hydroxylation in vitro. Drug Metab Dispos 2008;36:2513-22. doi: 10.1124/dmd.108.02297010.1124/dmd.108.022970Search in Google Scholar

15. Sakaguchi K, Green M, Stock N, Reger TS, Zunic J, King C. Glucuronidation of carboxylic acid containing compounds by UDP-glucuronosyltransferase isoforms. Arch Biochem Biophys. 2004;424(2):219-25. PMID: 15047194.10.1016/j.abb.2004.02.004Search in Google Scholar

16. Castillo M, Lam YW, Dooley MA, Stahl E, Smith PC. Disposition and covalent binding of ibuprofen and its acyl glucuronide in the elderly. Clin Pharmacol Ther 1995;57:636-44. doi: 10.1016/0009-9236(95)90226-010.1016/0009-9236(95)90226-0Search in Google Scholar

17. Grillo MP, Lohr MT, Khera S. Interaction of γ-glutamyltrans peptidase with ibuprofen-S-acyl-glutathione in vitro and in vivo in human. Drug Metab Dispos 2013;41:111-21. doi: 10.1124/dmd.112.04864510.1124/dmd.112.048645Search in Google Scholar

18. Tang W. The metabolism of diclofenac - enzymology and toxicology perspectives. Curr Drug Metab 2003;4:319-29. doi: 10.2174/138920003348939810.2174/1389200033489398Search in Google Scholar

19. Tang W, Stearns RA, Bandiera SM, Zhang Y, Raab C, Braun MP, Dean DC, Pang J, Leung KH, Doss GA, Strauss JR, Kwei GY, Rushmore TH, Chiu SH, Baillie TA. Studies on Cytochrome P-450-mediated bioactivation of diclofenac in rats and in human hepatocytes: identification of glutathione conjugated metabolites. Drug Metab Dispos 1999;27:365-72. PMID: 10064567Search in Google Scholar

20. King C, Tang W, Ngui J, Tephly T, Braun M. Characterization of rat and human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of diclofenac. Toxicol Sci 2001;61:49-53. doi: 10.1093/toxsci/61.1.4910.1093/toxsci/61.1.49Search in Google Scholar

21. Shipkova M, Armstrong VW, Oellerich M, Wieland E. Acyl glucuronide drug metabolites: toxicological and analytical implications. Ther Drug Monit 2003;25:1-16. PMID: 1254813810.1097/00007691-200302000-00001Search in Google Scholar

22. Bailey MJ, Dickinson RG. Acyl glucuronide reactivity in perspective: biological consequences. Chem Biol Interact 2003;145:117-37. doi: 10.1016/S0009-2797(03)00020-610.1016/S0009-2797(03)00020-6Search in Google Scholar

23. Deer TR, Leong MS, Buvanendran A. Comprehensive treatment of chronic pain by medical, interventional, and integrative approaches: the American Academy Of Pain Medicine textbook on patient management. New York (NY): Springer; 201310.1007/978-1-4614-1560-2Search in Google Scholar

24. King C, Tang W, Ngui J, Tephly T, Braun M. Characterization of rat and human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of diclofenac. Toxicol Sci 2001;61(1):49-53. PMID: 11294973.10.1093/toxsci/61.1.49Search in Google Scholar

25. Aithal GP, Ramsay L, Daly AK, Sonchit N, Leathart JB, Alexander G, Kenna JG, Caldwell J, Day CP. Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxicity. Hepatology 2004;39:1430-40. doi: 10.1002/hep.2020510.1002/hep.20205Search in Google Scholar

26. Sallustio BC, Sabordo L, Evans AM, Nation RL. Hepatic disposition of electrophilic acyl glucuronide conjugates. Curr Drug Metab 2000;1:163-80. PMID: 1146508110.2174/1389200003339153Search in Google Scholar

27. Lagas JS, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH. Hepatic clearance of reactive glucuronide metabolites of diclofenac in the mouse is dependent on multiple ATP-binding cassette efflux transporters. Mol Pharmacol 2010;77:687-94. doi: 10.1124/mol.109.06236410.1124/mol.109.062364Search in Google Scholar

28. Nies AT, Keppler D. The apical conjugate efflux pump ABCC2 (MRP2). Pflugers Arch 2007;453:643-59. doi: 10.1007/ s00424-006-0109-y10.1007/s00424-006-0109-ySearch in Google Scholar

29. Johansson I, Ingelman-Sundberg M. Genetic polymorphism and toxicology - with emphasis on Cytochrome p450. Toxicol Sci 2011;120:1-13. doi: 10.1093/toxsci/kfq37410.1093/toxsci/kfq374Search in Google Scholar

30. Sim SC, Kacevska M, Ingelman-Sundberg M. Pharmaco genomics of drug-metabolizing enzymes: a recent update on clinical implications and endogenous effects. Pharmaco genomics J 2013;13:1-11. doi: 10.1038/tpj.2012.4510.1038/tpj.2012.45Search in Google Scholar

31. Zhang D, Surapaneni S, editors. ADME-enabling technologies in drug design and development. Hoboken (NJ): Wiley; 2012.10.1002/9781118180778Search in Google Scholar

32. Agúndez JA, García-Martín E, Martínez C. Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine? Expert Opin Drug Metab Toxicol 2009;5:607-20. doi: 10.1517/1742525090 2970998Search in Google Scholar

33. Totah RA, Rettie AE. Cytochrome P450 2C8: substrates, inhibitors, pharmacogenetics, and clinical relevance. Clin Pharmacol Ther 2005;77:341-52. doi: 10.1016/j. clpt.2004.12.267Search in Google Scholar

34. Klose TS, Blaisdell JA, Goldstein JA. Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs. J Biochem Mol Toxicol 1999;13:289-95. PMID: 1048741510.1002/(SICI)1099-0461(1999)13:6<289::AID-JBT1>3.0.CO;2-NSearch in Google Scholar

35. The Human Cytochrome P450 (CYP) Allele Nomenclature Database [displayed 20 October 2015]. Available at http:// www.cypalleles.ki.se/ Search in Google Scholar

36. Daily EB, Aquilante CL. Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies. Pharmacogenomics 2009;10:1489-510. doi: 10.2217/pgs.09. 82Search in Google Scholar

37. Gao Y, Liu D, Wang H, Zhu J, Chen C. Functional characterization of five CYP2C8 variants and prediction of CYP2C8 genotype-dependent effects on in vitro and in vivo drug-drug interactions. Xenobiotica 2010;40:467-75. doi: 10.3109/00498254.2010.48716310.3109/00498254.2010.487163Search in Google Scholar

38. Paganotti GM, Gramolelli S, Tabacchi F, Russo G, Modiano D, Coluzzi M, Romano R. Distribution of human CYP2C8*2 allele in three different African populations. Malar J 2012;11:125. doi: 10.1186/1475-2875-11-12510.1186/1475-2875-11-125335323322531455Search in Google Scholar

39. Daly AK, Aithal GP, Leathart JB, Swainsbury RA, Dang TS, Day CP. Genetic susceptibility to diclofenac-induced hepatotoxicity: contribution of UGT2B7, CYP2C8, and ABCC2 genotypes. Gastroenterology 2007;132:272-81. doi: 10.1053/j.gastro.2006.11.02310.1053/j.gastro.2006.11.02317241877Search in Google Scholar

40. Wu X, Zuo J, Guo T, Yuan L. CYP2C8 polymorphism frequencies among Han, Uighur, Hui, and Mongolian Chinese populations. Genet Test Mol Biomarkers 2013;17:104-8. doi: 10.1089/gtmb.2012.025610.1089/gtmb.2012.025623336573Search in Google Scholar

41. Speed WC, Kang SP, Tuck DP, Harris LN, Kidd KK. Global variation in CYP2C8-CYP2C9 functional haplotypes. Pharmacogenomics J 2009;9:283-90. doi: 10.1038/tpj.2009.1010.1038/tpj.2009.10278240519381162Search in Google Scholar

42. López-Rodríguez R, Novalbos J, Gallego-Sandín S, Román- Martínez M, Torrado J, Gisbert JP, Abad-Santos F. Influence of CYP2C8 and CYP2C9 polymorphisms on pharmacokinetic and pharmacodynamic parameters of racemic and enantiomeric forms of ibuprofen in healthy volunteers. Pharmacol Res 2008;58:77-84. doi: 10.1016/j.phrs.2008.07.00410.1016/j.phrs.2008.07.00418694831Search in Google Scholar

43. Martínez C, García-Martín E, Blanco G, Gamito FJ, Ladero JM, Agúndez JA. The effect of the Cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects. Br J Clin Pharmacol 2005;59:62-9. doi: 10.1111/j.1365-2125.2004.02183.x10.1111/j.1365-2125.2004.02183.x188495915606441Search in Google Scholar

44. Garcia-Martin E, Martínez C, Tabarés B, Frías J, Agúndez JA. Interindividual variability in ibuprofen pharmacokinetics is related to interaction of Cytochrome P450 2C8 and 2C9 amino acid polymorphisms. Clin Pharmacol Ther 2004;76:119-27. doi: 10.1016/j.clpt.2004.04.00610.1016/j.clpt.2004.04.00615289789Search in Google Scholar

45. McGreavey LE, Turner F, Smith G, Boylan K, Timothy Bishop D, Forman D, Roland Wolf C, Barrett JH; Colorectal Cancer Study Group. No evidence that polymorphisms in CYP2C8, CYP2C9, UGT1A6, PPARdelta and PPARgamma act as modifiers of the protective effect of regular NSAID use on the risk of colorectal carcinoma. Pharmacogenet Genomics 2005;15:713-21. PMID: 1614179710.1097/01.fpc.0000174786.85238.6316141797Search in Google Scholar

46. Dorado P, Cavaco I, Cáceres MC, Piedade R, Ribeiro V, Llerena A. Relationship between CYP2C8 genotypes and diclofenac 5-hydroxylation in healthy Spanish volunteers. Eur J Clin Pharmacol 2008;64:967-70. doi: 10.1007/s00228-008-0508-410.1007/s00228-008-0508-418548238Search in Google Scholar

47. Benzon H, Raja SN, Fishman SE, Liu S, Cohen SP eds. Essentials of Pain Medicine. 3rd ed. Elsevier Health Sciences;Search in Google Scholar

2011.Search in Google Scholar

48. Aithal GP, Day CP. Nonsteroidal anti-inflammatory druginduced hepatotoxicity. Clin Liver Dis 2007;11:563-75. doi: 10.1016/j.cld.2007.06.00410.1016/j.cld.2007.06.00417723920Search in Google Scholar

49. O’Connor N, Dargan PI, Jones AL. Hepatocellular damage from non-steroidal anti-inflammatory drugs. QJM 2003;96:787-91. PMID: 14566034 10.1093/qjmed/hcg13814566034Search in Google Scholar

50. Aithal GP, Day CP, Leathart JB, Daly AK. Relationship of polymorphism in CYP2C9 to genetic susceptibility to diclofenac-induced hepatitis. Pharmacogenetics 2000;10:511-8. PMID: 1097560510.1097/00008571-200008000-0000410975605Search in Google Scholar

51. CYP2C9 allele nomenclature [displayed 20 October 2015]. Available at http://www.cypalleles.ki.se/cyp2c9.htmSearch in Google Scholar

52. Kirchheiner J, Meineke I, Freytag G, Meisel C, Roots I, Brockmöller J. Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofenpharmacokinetics and on the inhibition of cyclooxygenases 1 and 2. Clin Pharmacol Ther 2002;72:62-75. doi: 10.1067/mcp.2002.12572610.1067/mcp.2002.12572612152005Search in Google Scholar

53. Karaźniewicz-Łada M, Luczak M, Główka F. Pharmacokinetic studies of enantiomers of ibuprofen and its chiral metabolites in humans with different variants of genes coding CYP2C8 and CYP2C9 isoenzymes. Xenobiotica 2009;39:476-85. doi: 10.1080/0049825090286270510.1080/0049825090286270519480553Search in Google Scholar

54. Poon G. Ibuprofen lysine (NeoProfen) for the treatment of patent ductus arteriosus. Proc (Bayl Univ Med Cent) 2007;20(1):83-5.10.1080/08998280.2007.11928244176954117256050Search in Google Scholar

55. Durrmeyer X, Hovhannisyan S, Médard Y, Jacqz-Aigrain E, Decobert F, Barre J, Alberti C, Aujard Y, Danan C, Baud O.Search in Google Scholar

Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants? PLoS One 2010;5(8):e12329. doi: 10.1371/journal. pone.0012329 56.Search in Google Scholar

56. Zi J, Liu D, Ma P, Huang H, Zhu J, Wei D, Yang J, Chen C. Effects of CYP2C9*3 and CYP2C9*13 on diclofenac metabolism and inhibition-based drug-drug interactions. Drug Metab Pharmacokinet 2010;25:343-50. doi: 10.2133/dmpk. DMPK-10-RG-009Search in Google Scholar

57. Yasar U, Eliasson E, Forslund-Bergengren C, Tybring G, Gadd M, Sjöqvist F, Dahl ML The role of CYP2C9 genotype in the metabolism of diclofenac in vivo and in vitro. Eur J Clin Pharmacol 2001;57:729-35. doi: 10.1007/s00228-001-0376-710.1007/s00228-001-0376-711829203Search in Google Scholar

58. Pilotto A, Seripa D, Franceschi M, Scarcelli C, Colaizzo D, Grandone E, Niro V, Andriulli A, Leandro G, Di Mario F, Dallapiccola B. Genetic susceptibility to nonsteroidal antiinflammatory drug-related gastroduodenal bleeding: role of Cytochrome P450 2C9 polymorphisms. Gastroenterology 2007;133:465-71. doi: 10.1053/j.gastro.2007.05.02510.1053/j.gastro.2007.05.02517681167Search in Google Scholar

59. Ishihara M, Ohmiya N, Nakamura M, Funasaka K, Miyahara R, Ohno E, Kawashima H, Itoh A, Hirooka Y, Watanabe O, Ando T, Goto H. Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease. Aliment Pharmacol Ther 2014;40:538-47. doi: 10.1111/apt.1285810.1111/apt.1285825041257Search in Google Scholar

60. Node K, Huo Y, Ruan X, Yang B, Spiecker M, Ley K, Zeldin DC, Liao JK.Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science 1999;285 (5431):1276-9. PMID: 10455056;10.1126/science.285.5431.1276272002710455056Search in Google Scholar

61. Bellien J, Joannides R. Epoxyeicosatrienoic acid pathway in human health and diseases. J Cardiovasc Pharmacol 2013;61(3):188-96. doi: 10.1097/FJC.0b013e318273b00710.1097/FJC.0b013e318273b00723011468Search in Google Scholar

62. Fleming I, Michaelis UR, Bredenkötter D, Fisslthaler B, Dehghani F, Brandes RP, Busse R. Endothelium-derived hyperpolarizing factor synthase (Cytochrome P450 2C9) is a functionally significant source of reactive oxygen species in coronary arteries. Circ Res 2001;88(1):44-51. PMID: 11139472.10.1161/01.RES.88.1.44Search in Google Scholar

63. Stamer UM, Zhang L, Stuber F. Personalized therapy in pain management: where do we stand? Pharmacogenomics 2010;11:843-64. doi: 10.2217/pgs.10.47 10.2217/pgs.10.4720504256Search in Google Scholar

Englisch, Slovenian
Zeitrahmen der Veröffentlichung:
4 Hefte pro Jahr
Fachgebiete der Zeitschrift:
Medizin, Vorklinische Medizin, Grundlagenmedizin, andere