Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
JAMA. 2003 Sep 17;290(11):1500-4.

Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme.

Author information

  • 1Department of Pharmaceutical Sciences, Medical University of South Carolina, Institute of Psychiatry, Charleston 29425, USA. markowij@musc.edu

Abstract

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<.001) and a 2-fold increase in alprazolam clearance (P<.001) were observed following St John's wort administration. Alprazolam elimination half-life was shortened from a mean (SD) of 12.4 (3.9) hours to 6.0 (2.4) hours (P<.001). The mean (SD) urinary ratio of dextromethorphan to its metabolite was 0.006 (0.010) at baseline and 0.014 (0.025) after St John's wort administration (P =.26).

CONCLUSIONS:

A 14-day course of St John's wort administration significantly induced the activity of CYP 3A4 as measured by changes in alprazolam pharmacokinetics. This suggests that long-term administration of St John's wort may result in diminished clinical effectiveness or increased dosage requirements for all CYP 3A4 substrates, which represent at least 50% of all marketed medications.

Comment in

PMID:
13129991
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems
    Loading ...
    Write to the Help Desk