OpenLB
Open Library of Bioscience
Advanced Search
CPT: pharmacometrics & systems pharmacology
Mar 26, 2014;3 e107.

Physiologically based pharmacokinetic modeling framework for quantitative prediction of an herb-drug interaction.

S J Brantley, B T Gufford, R Dua, D J Fediuk, T N Graf, Y V Scarlett, K S Frederick, M B Fisher, N H Oberlies, M F Paine
Author Information
  1. S J Brantley: Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  2. B T Gufford: College of Pharmacy, Washington State University, Spokane, Washington, USA.
  3. R Dua: Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  4. D J Fediuk: Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  5. T N Graf: Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, North Carolina, USA.
  6. Y V Scarlett: School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  7. K S Frederick: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA.
  8. M B Fisher: ProPharma Services, LLC, Oxford, Connecticut, USA.
  9. N H Oberlies: Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, North Carolina, USA.
  10. M F Paine: College of Pharmacy, Washington State University, Spokane, Washington, USA.
PMID: 24670388 DOI: 10.1038/psp.2013.69

Abstract

Herb-drug interaction predictions remain challenging. Physiologically based pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of potential herb-drug interactions using the semipurified milk thistle preparation, silibinin, as an exemplar herbal product. Interactions between silibinin constituents and the probe substrates warfarin (CYP2C9) and midazolam (CYP3A) were simulated. A low silibinin dose (160 mg/day × 14 days) was predicted to increase midazolam area under the curve (AUC) by 1%, which was corroborated with external data; a higher dose (1,650 mg/day × 7 days) was predicted to increase midazolam and (S)-warfarin AUC by 5% and 4%, respectively. A proof-of-concept clinical study confirmed minimal interaction between high-dose silibinin and both midazolam and (S)-warfarin (9 and 13% increase in AUC, respectively). Unexpectedly, (R)-warfarin AUC decreased (by 15%), but this is unlikely to be clinically important. Application of this PBPK modeling framework to other herb-drug interactions could facilitate development of guidelines for quantitative prediction of clinically relevant interactions.CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e107; doi:10.1038/psp.2013.69; advance online publication 26 March 2014.

References

  1. Pharmacogenetics. 1996 Aug;6(4):341-9 [PMID: 8873220]
  2. J Pharm Sci. 2001 Apr;90(4):436-47 [PMID: 11170034]
  3. Toxicol In Vitro. 2011 Feb;25(1):21-7 [PMID: 20828605]
  4. J Clin Pharmacol. 2000 Aug;40(8):826-35 [PMID: 10934666]
  5. J Clin Pharmacol. 2010 Apr;50(4):434-49 [PMID: 19841158]
  6. Drug Metab Dispos. 2004 Jun;32(6):587-94 [PMID: 15155549]
  7. J Clin Pharmacol. 2006 Feb;46(2):201-13 [PMID: 16432272]
  8. Br J Clin Pharmacol. 1994 Jun;37(6):563-9 [PMID: 7917775]
  9. Pharm Res. 2008 Aug;25(8):1807-14 [PMID: 18236139]
  10. J Pharm Sci. 2001 Sep;90(9):1226-41 [PMID: 11745776]
  11. Front Pharmacol. 2011 Nov 10;2:56 [PMID: 22084631]
  12. Drug Metab Dispos. 2008 Sep;36(9):1786-93 [PMID: 18515332]
  13. Clin Pharmacol Ther. 1998 Sep;64(3):269-77 [PMID: 9757150]
  14. Expert Opin Drug Metab Toxicol. 2007 Feb;3(1):67-80 [PMID: 17269895]
  15. Clin Pharmacol Ther. 1995 Dec;58(6):641-9 [PMID: 8529329]
  16. Phytother Res. 2002 Nov;16(7):632-8 [PMID: 12410543]
  17. Teratology. 1994 Feb;49(2):90-103 [PMID: 8016750]
  18. Planta Med. 2007 Nov;73(14):1495-501 [PMID: 17948171]
  19. Eur J Clin Pharmacol. 2009 Jun;65(6):585-91 [PMID: 19221727]
  20. Clin Pharmacokinet. 2010 Mar;49(3):189-206 [PMID: 20170207]
  21. J Clin Pharmacol. 1999 Jul;39(7):664-9 [PMID: 10392320]
  22. Drug Metab Dispos. 2008 Jan;36(1):65-72 [PMID: 17913795]
  23. Org Biomol Chem. 2003 May 21;1(10):1684-9 [PMID: 12926355]
  24. Chirality. 1991;3(1):24-9 [PMID: 2039681]
  25. Br J Clin Pharmacol. 1987 Mar;23(3):273-8 [PMID: 3567042]
  26. Drug Metab Dispos. 2013 Sep;41(9):1662-70 [PMID: 23801821]
  27. Curr Top Med Chem. 2011;11(4):334-9 [PMID: 21320062]
  28. J Pharmacol Exp Ther. 2010 Mar;332(3):1081-7 [PMID: 19934397]
  29. Drug Metab Dispos. 2009 Mar;37(3):514-22 [PMID: 19114462]
  30. Drug Metab Dispos. 2009 Aug;37(8):1658-66 [PMID: 19406954]
  31. J Clin Pharmacol. 2004 Jun;44(6):570-6 [PMID: 15145963]
  32. Clin Pharmacol Ther. 2012 Nov;92(5):651-7 [PMID: 23047652]
  33. Clin Pharmacol Ther. 2004 Nov;76(5):428-40 [PMID: 15536458]
  34. Radiat Prot Dosimetry. 2003;105(1-4):571-4 [PMID: 14527029]
  35. Cancer Res. 2005 May 15;65(10):4448-57 [PMID: 15899838]
  36. J Exp Pharmacol. 2010 Jul;2010(2):83-91 [PMID: 20865058]
  37. Curr Drug Metab. 2007 Jan;8(1):33-45 [PMID: 17266522]
  38. Planta Med. 2012 Sep;78(13):1458-77 [PMID: 22855269]
  39. Planta Med. 2012 Sep;78(13):1478-89 [PMID: 22322396]
  40. Planta Med. 2012 Sep;78(13):1400-15 [PMID: 22864989]
  41. Clin Pharmacol Ther. 2012 Mar;91(3):542-9 [PMID: 22318616]
  42. Integr Cancer Ther. 2007 Jun;6(2):110-9 [PMID: 17548790]
  43. Hepatogastroenterology. 1998 Jul-Aug;45(22):1069-74 [PMID: 9756008]
  44. J Nat Prod. 2010 Apr 23;73(4):613-9 [PMID: 20297826]

Grants

  1. R01 GM077482/NIGMS NIH HHS
  2. UL1 TR000083/NCATS NIH HHS
Journal Article

Word Cloud

Created with Highcharts 10.0.0silibininmidazolamAUCinteractionmodelingpredictionherb-druginteractionsincrease-warfarinPhysiologicallybasedpharmacokineticPBPKdose×dayspredictedSrespectivelyclinicallyframeworkquantitative2014Herb-drugpredictionsremainchallengingusedimproveaccuracypotentialusingsemipurifiedmilkthistlepreparationexemplarherbalproductInteractionsconstituentsprobesubstrateswarfarinCYP2C9CYP3Asimulatedlow160 mg/day14areacurve1%corroboratedexternaldatahigher1650 mg/day75%4%proof-of-conceptclinicalstudyconfirmedminimalhigh-dose913%UnexpectedlyRdecreased15%unlikelyimportantApplicationfacilitatedevelopmentguidelinesrelevantCPTPharmacometricsSystPharmacol3e107doi:101038/psp201369advanceonlinepublication26March

Similar Articles

Cited By