Effect of St John's Wort on Drug Metabolism by Induction of Cytochrome P450 3A4 Enzyme

CONTEXT St John's wort is a popular herbal product used to treat depression but it has been implicated in drug interactions. OBJECTIVE To assess the potential of St John's wort administration to alter the activity of the cytochrome P450 (CYP) enzymes extensively involved in drug metabolism. DESIGN, SETTING, AND PARTICIPANTS Open-label crossover study with fixed treatment order conducted March 2002 to February 2003 in a US general clinical research center involving 12 healthy volunteers (6 men and 6 women) aged 22 to 38 years before and after 14 days of administration of St John's wort. INTERVENTION Participants were given probe drugs (30 mg of dextromethorphan and 2 mg of alprazolam) to establish baseline CYP 3A4 and CYP 2D6 activity. After a minimum 7-day washout period, participants began taking one 300-mg tablet 3 times per day. After 14 days of St John's wort administration, participants were given the probe drugs along with 1 St John's wort tablet to establish postadministration CYP activity; the St John's wort dosing regimen was continued for 48 hours. MAIN OUTCOME MEASURES Changes in plasma pharmacokinetics of alprazolam as a probe for CYP 3A4 activity and the ratio of dextromethorphan to its metabolite, dextrorphan, in urine as a probe for CYP 2D6 activity. RESULTS A 2-fold decrease in the area under the curve for alprazolam plasma concentration vs time (P