St John's Wort: Effect on CYP3A4 activity

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‐β‐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‐β‐hydroxycortisol/cortisol ratio after a 24–hour urine collection. Results The mean ± SD urinary 6‐β‐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‐β‐hydroxycortisol/cortisol ratio. This finding suggests that St John's Wort is an inducer of CYP3A4. Clinical Pharmacology & Therapeutics (2000) 67 , 451–457; doi: 10.1067/mcp.2000.106793