alexa St John's Wort: effect on CYP3A4 activity.
Clinical Research

Clinical Research

Journal of Clinical Trials

Author(s): Roby CA, Anderson GD, Kantor E, Dryer DA

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BACKGROUND: St John's Wort is a widely used herbal product. Information regarding its potential for drug interactions is required for responsible treatment of patients using St John's Wort. CYP3A4 is a metabolic enzyme implicated in most clinically significant drug-drug interactions. OBJECTIVE: To determine the in vivo effect of reagent-grade St John's Wort extract on CYP3A4 activity through evaluation of urinary 6-beta-hydroxycortisol/cortisol ratios. METHODS: Thirteen subjects ranging in age from 18 to 25 years participated in this unblinded, multiple-dose, single-treatment before-after trial conducted in a university-based pharmacokinetics and biopharmaceutics laboratory. Each subject ingested a 300-mg tablet of reagent-grade St John's Wort extract standardized to 0.3% hypericin three times a day for 14 days. Baseline and posttreatment CYP3A4 activity was assessed with the urinary 6-beta-hydroxycortisol/cortisol ratio after a 24-hour urine collection. RESULTS: The mean +/- SD urinary 6-beta-hydroxycortisol/cortisol ratio significantly increased (P = .003) from a baseline value of 7.1 +/- 4.5 to 13 +/- 4.9. The mean +/- SD percentage increase was 114% +/- 95%, with a range from -25% to 259%. All but one subject had an increase in the ratio. CONCLUSIONS: Treatment with St John's Wort for 14 days resulted in significant increases in the urinary 6-beta-hydroxycortisol/cortisol ratio. This finding suggests that St John's Wort is an inducer of CYP3A4.

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This article was published in Clinical pharmacology and therapeutics. and referenced in Journal of Clinical Trials

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