Display options
Cite
Wei Y, Tang C, Sant V, et al. A Molecular Aspect in the Regulation of Drug Metabolism: Does PXR-Induced Enzyme Expression Always Lead to Functional Changes in Drug Metabolism?. Curr Pharmacol Rep. 2016;2(4):187-192doi: 10.1007/s40495-016-0062-1.
Wei, Y., Tang, C., Sant, V., Li, S., Poloyac, S. M., & Xie, W. (2016). A Molecular Aspect in the Regulation of Drug Metabolism: Does PXR-Induced Enzyme Expression Always Lead to Functional Changes in Drug Metabolism?. Current pharmacology reports, 2(4), 187-192. https://doi.org/10.1007/s40495-016-0062-1
Wei, Yuan, et al. "A Molecular Aspect in the Regulation of Drug Metabolism: Does PXR-Induced Enzyme Expression Always Lead to Functional Changes in Drug Metabolism?." Current pharmacology reports vol. 2,4 (2016): 187-192. doi: https://doi.org/10.1007/s40495-016-0062-1
Wei Y, Tang C, Sant V, Li S, Poloyac SM, Xie W. A Molecular Aspect in the Regulation of Drug Metabolism: Does PXR-Induced Enzyme Expression Always Lead to Functional Changes in Drug Metabolism?. Curr Pharmacol Rep. 2016 Aug;2(4):187-192. doi: 10.1007/s40495-016-0062-1. Epub 2016 May 04. PMID: 27795941; PMCID: PMC5082989.
Copy Download .nbib Format: NLM
Share it on

Curr Pharmacol Rep. 2016 Aug;2(4):187-192. doi: 10.1007/s40495-016-0062-1. Epub 2016 May 04.

A Molecular Aspect in the Regulation of Drug Metabolism: Does PXR-Induced Enzyme Expression Always Lead to Functional Changes in Drug Metabolism?.

Current pharmacology reports

Yuan Wei, Chenxiao Tang, Vinayak Sant, Song Li, Samuel M Poloyac, Wen Xie

Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 306 Salk Pavilion, 335 Sutherland Drive, Pittsburgh, PA 15261, USA.

PMID: 27795941 PMCID: PMC5082989 DOI: 10.1007/s40495-016-0062-1

Abstract

Pregnane X receptor (PXR, NR112) is a xenobiotic receptor whose primary function is to regulate the expression of drug-metabolizing enzymes (DMEs) and drug transporters. Drug-induced PXR activation and subsequent enzyme and transporter induction has been proposed to be an important mechanism for the drug-drug interactions. In addition to activating PXR, many pharmaceutical chemicals can also function as reversible or irreversible inhibitors of DMEs, which may also impact the pharmacokinetics and pharmacodynamics (PK/PD) of drugs. Therefore, we cannot simply conclude that the PXR-induced alteration in enzyme expression always reflects functional changes. We should consider both PXR activation and DMEs inhibition to improve drug safety in the clinic.

Keywords: Drug metabolism; Enzyme inhibition; Gene regulation; Nuclear receptor

References

  1. Phytomedicine. 2010 Sep;17(11):868-75 - PubMed
  2. Int J Pharm. 2010 Apr 15;389(1-2):114-21 - PubMed
  3. J Biol Chem. 1995 Dec 1;270(48):28917-23 - PubMed
  4. Biochem Pharmacol. 2015 Oct 1;97(3):320-30 - PubMed
  5. Chem Biol Interact. 2015 Jan 25;226:23-9 - PubMed
  6. Xenobiotica. 2012 Dec;42(12):1163-9 - PubMed
  7. Gastroenterology. 2011 Jun;140(7):2095-106 - PubMed
  8. Drug Metab Dispos. 2001 May;29(5):615-22 - PubMed
  9. Chem Biol Interact. 2012 Jun 25;198(1-3):49-56 - PubMed
  10. Clin Pharmacokinet. 2005;44(3):279-304 - PubMed
  11. Mol Pharmacol. 2007 Jan;71(1):220-9 - PubMed
  12. Genes Dev. 1998 May 1;12(9):1269-77 - PubMed
  13. Annu Rev Pharmacol Toxicol. 1983;23:481-503 - PubMed
  14. Drug Discov Today. 2004 May 15;9(10):442-9 - PubMed
  15. Genes Dev. 2000 Dec 1;14 (23 ):3014-23 - PubMed
  16. Nat Med. 2013 Apr;19(4):418-20 - PubMed
  17. Chem Res Toxicol. 2009 Jul;22(7):1298-309 - PubMed
  18. J Proteome Res. 2013 Mar 1;12(3):1359-68 - PubMed
  19. BMC Biochem. 2010 Jun 16;11:23 - PubMed
  20. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010 Jun;154(2):103-16 - PubMed
  21. Clin Pharmacol Ther. 2011 Apr;89(4):579-86 - PubMed
  22. Drug Discov Today Technol. 2013 Spring;10(1):e177-89 - PubMed
  23. Chem Biol Interact. 2014 May 25;215:62-8 - PubMed
  24. Trends Pharmacol Sci. 2001 Sep;22(9):448 - PubMed
  25. Toxicol Appl Pharmacol. 2013 Jan 1;266(1):122-31 - PubMed
  26. Drug Metab Dispos. 2003 Nov;31(11):1352-60 - PubMed
  27. Cancer Lett. 2013 Jan 1;328(1):1-9 - PubMed
  28. Annu Rev Pharmacol Toxicol. 1999;39:1-17 - PubMed
  29. Biopharm Drug Dispos. 2010 May;31(4):264-8 - PubMed
  30. Biochem Pharmacol. 2012 Apr 15;83(8):1112-26 - PubMed
  31. Drug Metab Dispos. 2011 Jul;39(7):1188-95 - PubMed
  32. Drug Metab Dispos. 2013 May;41(5):1012-22 - PubMed
  33. Clin Pharmacokinet. 1998 Nov;35(5):361-90 - PubMed
  34. Cell. 1998 Jan 9;92 (1):73-82 - PubMed
  35. Nat Rev Drug Discov. 2002 Apr;1(4):259-66 - PubMed
  36. Curr Opin Drug Discov Devel. 2010 Jan;13(1):66-77 - PubMed
  37. Drug Metab Dispos. 2009 Mar;37(3):629-34 - PubMed
  38. J Biol Chem. 1983 Apr 10;258(7):4202-7 - PubMed
  39. Drug Metab Dispos. 2010 Dec;38(12):2091-5 - PubMed
  40. Arch Toxicol. 2008 Oct;82(10):667-715 - PubMed
  41. Science. 2001 Jun 22;292(5525):2329-33 - PubMed
  42. Curr Drug Metab. 2007 Jun;8(5):407-47 - PubMed
  43. Chem Res Toxicol. 1990 Jul-Aug;3(4):363-71 - PubMed
  44. Mol Pharmacol. 1999 Nov;56(5):851-7 - PubMed
  45. J Pharmacol Exp Ther. 1999 Feb;288(2):791-7 - PubMed
  46. Annu Rev Pharmacol Toxicol. 2002;42:1-23 - PubMed
  47. Biol Pharm Bull. 2012;35(3):329-34 - PubMed
  48. Drug Metab Dispos. 2015 Jan;43(1):82-8 - PubMed
  49. Phytother Res. 2011 Aug;25(8):1250-3 - PubMed
  50. Genes Dev. 1998 Oct 15;12(20):3195-205 - PubMed
  51. J Pharmacol Exp Ther. 2002 Apr;301(1):160-7 - PubMed
  52. Curr Drug Metab. 2005 Jun;6(3):241-57 - PubMed
  53. J Pharmacol Exp Ther. 2006 Mar;316(3):1369-77 - PubMed
  54. Antimicrob Agents Chemother. 2008 Apr;52(4):1291-6 - PubMed
  55. Drug Metab Dispos. 2010 Dec;38(12):2286-92 - PubMed
  56. Drug Metab Dispos. 2014 Jan;42(1):193-9 - PubMed
  57. FASEB J. 1988 Sep;2(12):2774-83 - PubMed

Publication Types

Grant support