title: Ganoderic acid B's influence towards the therapeutic window of trifluoperazine (TFP).
abstract: BACKGROUND
  Ganoderic acid B is an important bioactive ingredient isolated from Ganoderma lucidum, and exhibits various pharmacological activities.
  
  
  OBJECTIVE
  To investigate the influence of Ganoderic acid B towards the therapeutic window of trifluoperazine (TFP).
  
  
  METHODS
  In vitro human liver microsomes (HLMs) incubation system was used to determine the inhibition of Ganoderic acid B towards the glucuronidation of trifluoperazine (TFP).
  
  
  RESULTS
  Ganoderic acid B exerted concentration-dependent inhibition towards the glucuronidation of TFP. Furthermore, Dixon plot was used to determine the inhibition type. The intersection point was located in the second quadrant in Dixon plot, indicating the competitive inhibition of Ganoderic acid B towards TFP glucuronidation. Through fitting the data using competitive nonlinear fitting equation, the inhibition kinetic parameter was calculated to be 56.7 uM.
  
  
  CONCLUSIONS
  All this data indicated the potential influence of Ganoderic acid B-containing herbs towards therapeutic window of TFP. Given that the glucuronidation reaction of TFP is the probe reaction of UGT1A4, the data obtained from the present study also indicated the potential influence of Ganoderic acid-containing herbs towards the therapeutic window of drugs mainly undergoing UGT1A4-mediated metabolism.
authors.affiliation: Department of Neurology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Laboratory of Pharmacology, Department of Pharmacy, Jinan Military General Hospital, Jinan 250031, P.R. China.
authors.forename: Chenming
authors.initials: C
authors.lastname: Ni
authors.affiliation: Department of Hepatobiliary Surgery, Jinan Military General Hospital, Jinan 250031, P.R. China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
mesh_terms: D018492:Dopamine Antagonists; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D006923:Hymecromone / Q000031:analogs & derivatives / Q000378:metabolism; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D011134:Polysaccharides; D013261:Sterols; D014268:Trifluoperazine / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018492:Dopamine Antagonists; D011134:Polysaccharides; D013261:Sterols; D014268:Trifluoperazine; D006923:Hymecromone; C476673:ganoderic acid B; D014453:Glucuronosyltransferase
keywords: Ganoderic acid B; UDP-glucuronosyltransferase (UGT) 1A4; trifluoperazine (TFP)
references.citation: Curr Drug Metab. 2000 Sep;1(2):143-61
references.pmid: 11465080
references.citation: Endocrinology. 2014 Jun;155(6):2052-63
references.pmid: 24641623
references.citation: Drug Metab Dispos. 1995 Mar;23(3):299-302
references.pmid: 7628292
references.citation: Drug Metab Dispos. 2006 Mar;34(3):449-56
references.pmid: 16381668
references.citation: Br J Clin Pharmacol. 2010 Feb;69(2):193-9
references.pmid: 20233183
references.citation: Drug Metab Dispos. 2011 Jul;39(7):1127-30
references.pmid: 21487055
references.citation: Fitoterapia. 2012 Mar;83(2):408-14
references.pmid: 22178684
references.citation: Int J Clin Pharmacol Ther. 2012 Oct;50(10):712-21
references.pmid: 22762853
references.citation: Biomed Chromatogr. 2013 Sep;27(9):1177-87
references.pmid: 23723086
references.citation: Pharm Res. 2013 Sep;30(9):2174-87
references.pmid: 23462933
references.citation: Mol Nutr Food Res. 2013 Oct;57(10):1892-6
references.pmid: 23610080
references.citation: Neuropharmacology. 2013 Dec;75:365-79
references.pmid: 23954492
references.citation: Br J Pharmacol. 2014 Apr;171(7):1735-46
references.pmid: 24417285
references.citation: Toxicol Appl Pharmacol. 2014 May 15;277(1):86-94
references.pmid: 24631340
references.citation: Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12671-6
references.pmid: 11606755