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The Effect of St John’s Wort on the Pharmacokinetics of Docetaxel

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Abstract

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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Acknowledgments

This work was supported by the Dutch Cancer Society [UU 2007-3795].

Conflict of Interest Disclosure Statement

The authors have no conflicts of interest that are directly relevant to the content of this article.

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Author notes

  1. Andrew K. L. Goey

    Present address: Clinical Pharmacology Program, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA

Authors and Affiliations

  1. Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Andrew K. L. Goey, Jos H. Beijnen & Jan H. M. Schellens

  2. Division of Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Irma Meijerman

  3. Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Hilde Rosing & Jos H. Beijnen

  4. Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Serena Marchetti, Marja Mergui-Roelvink, Marianne Keessen & Jan H. M. Schellens

  5. Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Jacobus A. Burgers

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Correspondence to Andrew K. L. Goey.

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Goey, A.K.L., Meijerman, I., Rosing, H. et al. The Effect of St John’s Wort on the Pharmacokinetics of Docetaxel. Clin Pharmacokinet 53, 103–110 (2014). https://doi.org/10.1007/s40262-013-0102-5

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