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The effect of St John's wort on the pharmacokinetics of docetaxel
Andrew K L Goey1, Irma Meijerman, Hilde Rosing
1Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands, andrew.goey@nih.gov.
Background And Objective:
St John's wort (SJW), a herbal antidepressant, is commonly used by cancer patients, and its component hyperforin is a known inducer of the cytochrome P450 (CYP) isoenzyme 3A4. Here, the potential pharmacokinetic interaction between SJW and the sensitive CYP3A4 substrate docetaxel was investigated.
Methods:
In ten evaluable cancer patients, the pharmacokinetics of docetaxel (135 mg administered intravenously over 60 min) were compared before and after 14 days of supplementation with SJW (300 mg extract [Hyperiplant(®)] three times daily).
Results:
SJW supplementation resulted in a statistically significant decrease in the mean area under the docetaxel plasma concentration-time curve extrapolated to infinity (AUC∞) from 3,035 ± 756 to 2,682 ± 717 ng · h/mL (P = 0.045). Furthermore, docetaxel clearance significantly increased from 47.2 to 53.7 L/h (P = 0.045) after SJW intake. The maximum plasma concentration and elimination half-life of docetaxel were (non-significantly) decreased after SJW supplementation. In addition, the incidence of docetaxel-related toxicities was lower after SJW supplementation.
Conclusion:
These results suggest that concomitant use of docetaxel and the applied SJW product should be avoided to prevent potential undertreatment of cancer patients.
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