title: Effects of herbal supplements on the bioactivation of chemotherapeutic agents.
abstract: OBJECTIVE
  The aim of this study was to investigate the impact of commercially available, over-the-counter herbal supplements (St John's wort, black cohosh and ginger root extract) on the metabolic activation of tamoxifen and irinotecan.
  
  
  METHODS
  Co-incubation of each drug and supplement combination over a range of concentrations was conducted in human liver microsomes and the decrease in the rate of active metabolite formation was monitored using high-performance liquid chromatography tandem mass spectrometry. Data was analysed using non-linear regression analysis and Dixon plots to determine the dominant mechanism of inhibition and to estimate the Ki and IC50 values of the commercial supplements.
  
  
  RESULTS
  The data suggest that black cohosh was the strongest inhibitor tested in this study for both CYP450 and carboxyesterase mediated biotransformation of tamoxifen and irinotecan, respectively, to their active metabolites. St John's wort was a stronger inhibitor compared with ginger root extract for tamoxifen (CYP mediated pathway), while ginger root extract was a stronger inhibitor compared with St John's wort for the carboxyesterase mediated pathway.
  
  
  CONCLUSIONS
  Commercially available supplements are widely used by patients and their potential impact on the efficacy of the chemotherapy is often unknown. The clinical significance of these results needs to be evaluated in a comprehensive clinical trial.
authors.affiliation: McWhorter School of Pharmacy, Samford University, Birmingham, AL 35229, USA. ggorman@samford.edu
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Gorman
authors.forename: Lori
authors.initials: L
authors.lastname: Coward
authors.forename: Adrienne
authors.initials: A
authors.lastname: Darby
authors.forename: Bethany
authors.initials: B
authors.lastname: Rasberry
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000378:metabolism; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D043182:Carboxylesterase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D031885:Cimicifuga / Q000737:chemistry; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D020939:Zingiber officinale / Q000737:chemistry; D006801:Humans; D020902:Hypericum / Q000737:chemistry; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D012044:Regression Analysis; D013629:Tamoxifen / Q000008:administration & dosage / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D013629:Tamoxifen; D000077146:Irinotecan; D003577:Cytochrome P-450 Enzyme System; D043182:Carboxylesterase; D002166:Camptothecin