Article

Assessing the Clinical Significance of Botanical Supplementation on Human Cytochrome P450 3A Activity: Comparison of a Milk Thistle and Black Cohosh Product to Rifampin and Clarithromycin

University of Arkansas at Little Rock, Little Rock, Arkansas, United States
The Journal of Clinical Pharmacology (Impact Factor: 2.48). 03/2006; 46(2):201-13. DOI: 10.1177/0091270005284854
Source: PubMed

ABSTRACT

Phytochemical-mediated modulation of cytochrome P450 enzymes (CYPs) may underlie many herb-drug interactions. This study's purpose was to assess the effects of milk thistle and black cohosh supplementation on CYP3A activity and compare them to a clinically recognized inducer, rifampin, and inhibitor, clarithromycin. Healthy volunteers were randomly assigned to receive a standardized milk thistle (900 mg) or black cohosh (80 mg) supplement for 14 days. Subjects also received rifampin (600 mg) and clarithromycin (1000 mg) for 7 days as positive controls for CYP3A induction and inhibition, respectively. Midazolam was administered orally before and after each supplementation and control period. The effects of milk thistle, black cohosh, rifampin, and clarithromycin on midazolam pharmacokinetics were determined using noncompartmental techniques. Unlike those observed for rifampin and clarithromycin, midazolam pharmacokinetics was unaffected by milk thistle or black cohosh. Milk thistle and black cohosh appear to have no clinically relevant effect on CYP3A activity in vivo.

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Available from: Bill Gurley, Sep 24, 2014
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    • "In a human interaction study, CR (80 mg) was given over 14 days to 19 healthy subjects . No clinically relevant interaction with CYP3A4 could be demonstrated using midazolam as the test drug (Gurley et al. 2006a). In MDA-MB-453 and MCF-7 human breast cancer cells, CYP1A1, CYP1B1 (Einbond et al. 2007; Gaube et al. 2007) and ABCC3 (MRP3) (Einbond et al. 2007) were up-regulated. "
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    • "Moreover, it has been shown by an in vitro study that certain triterpene glycosides isolated from black cohosh only weakly inhibited human CYP3A4 (Tsukamoto et al., 2005). This is in agreement with in vivo data suggesting no clinically significant interactions between black cohosh and CYP3A4 (Gurley et al., 2005Gurley et al., , 2006). Because hot flashes are the main indication for black cohosh use, women who experience this side effect of tamoxifen may decide to use black cohosh as a presumably safe remedy. "
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    ABSTRACT: Export Date: 18 October 2014
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