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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans.

OBJECTIVES: Phytochemical-mediated modulation of cytochrome P450 ( CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of St John's wort, garlic oil, Panax ginseng, and Ginkgo biloba affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity. METHODS: Twelve healthy volunteers (6 females) were randomly assigned to receive either St John's wort, garlic oil, P ginseng, or G biloba for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe-drug cocktails of midazolam, caffeine, chlorzoxazone, and debrisoquin (INN, debrisoquine) were administered before supplementation (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4, CYP1A2, CYP2E1, and CYP2D6 with the use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. RESULTS: Comparisons of presupplementation and postsupplementation ratios indicated that St John's wort significantly induced the activity of CYP2E1 and CYP3A4 (P <.0001). Among female subjects, St John's wort produced significantly greater increases in CYP3A4 phenotypic ratios that appeared to be unrelated to body mass index. This finding is suggestive of a sexual dimorphism in CYP3A4 inducibility. Garlic oil reduced CYP2E1 activity by 39% (P =.030), whereas no significant effect on CYP activity was observed for P ginseng and G biloba. CONCLUSIONS: Single-time point phenotypic metabolic ratios may provide a practical means of predicting CYP-mediated herb-drug interactions in humans.[1]


  1. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Gurley, B.J., Gardner, S.F., Hubbard, M.A., Williams, D.K., Gentry, W.B., Cui, Y., Ang, C.Y. Clin. Pharmacol. Ther. (2002) [Pubmed]
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