title: [The inhibition of CYP2C9 isoenzyme in Cunninghamella blakesleeana AS 3. 910].
abstract: OBJECTIVE
  To investigate the variation of CYP2C9 isoenzyme activity in the microbial model in response to inhibitors of CYP2C9.
  
  
  METHODS
  Using C. blakesleeana AS 3. 910 as a model strain, the impact of CYP2C9 inhibitors on the metabolites yields of CYP2C9 substrates was determined and the drug-drug interactions among CYP2C9 substrates were evaluated. Liquid chromatography-mass spectrometry was used to analyze biotransformation products.
  
  
  RESULTS
  Benzbromarone decreased the yield of 4'-hydroxytolbutamide from 100% to 14.5%; sulfaphenazole decreased the yield of O-demethylindomethacin from 75.2% to 9.9%; valproic acid decreased the yield of 4'-hydroxydiclofenac from 98.6% to 2.7%, separately. Tolbutamide, indomethacin and diclofenac interacted with each other, resulting in the decreased formation of metabolites catalyzed by CYP2C9.
  
  
  CONCLUSIONS
  Three CYP2C9 inhibitors inhibit the activity of CYP2C9 isoenzyme in C. blakesleeana AS 3. 910 differently, and there are drug-drug interactions among CYP2C9 substrates.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Lin
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Huang
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Da-Fang
authors.initials: DF
authors.lastname: Zhong
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001553:Benzbromarone / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D002384:Catalysis / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D020093:Cunninghamella / Q000201:enzymology / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9; D004008:Diclofenac / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013379:Substrate Specificity; D013426:Sulfaphenazole / Q000494:pharmacology; D014044:Tolbutamide / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: C516573:4'-hydroxytolbutamide; D005656:Fungal Proteins; D007527:Isoenzymes; D013426:Sulfaphenazole; D004008:Diclofenac; D001553:Benzbromarone; D014635:Valproic Acid; D014044:Tolbutamide; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C108036:4'-hydroxydiclofenac; D007213:Indomethacin