Research: ROBY and colleagues, Depa

Listed in Issue 56

Abstract

ROBY and colleagues, Department of Pharmacy, St Agnes Hospital, University of Maryland, Baltimore, USA conducted a clinical trial of the effect of St John's Wort on the activity of the metabolic enzyme CYP3A4.

Background

St John's Wort is a widely used herbal product. Our knowledge 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. The aim of this study was 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.

Methodology

Thirteen subjects (18 to 25 years old) participated in this open, multiple-dose, single-treatment before-after trial conducted in a university-based laboratory. Each subject was asked to ingest 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 post-treatment CYP3A4 activity was assessed with the urinary 6-beta-hydroxycortisol/cortisol ratio after a 24-hour urine collection.

Results

The mean urinary 6-beta-hydroxycortisol/cortisol ratio significantly increased from 7.1 +/- 4.5 (baseline) to 13 +/- 4.9 (P = 0.003). The mean percentage increase was 114% +/- 95%, with a range from -25% to 259%. All but one subject had an increase in the ratio.

Conclusion

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.

References

Roby CA et al. St John's Wort: effect on CYP3A4 activity. Clinical Pharmacology and Therapeutics 67(5): 451-7. May 2000.

Comment

With the increasing use of herbal medicines, this study highlights the importance of studying potential interaction with conventional medicines.

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