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Lack of pharmacokinetic interaction between fluvastatin and green tea in healthy volunteers

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The objective of this study is to assess the effects of green tea and its major catechin component, (−)-epigallocatechin gallate (EGCG), on CYP2C9-mediated substrate metabolism in vitro, and the pharmacokinetics of fluvastatin in healthy volunteers.

Methods

The metabolism of diclofenac and fluvastatin in human recombinant CYP2C9 was investigated in the presence of EGCG. In a randomized three-phase crossover study, 11 healthy volunteers ingested a single 20-mg dose of fluvastatin with green tea extract (GTE), containing 150 mg of EGCG, along with water (300 mL), brewed green tea (300 mL), or water (300 mL) after overnight fasting. Plasma concentrations of fluvastatin and EGCG were measured by ultra-performance liquid chromatography with fluorescence detection and a single mass spectrometer.

Results

EGCG inhibited diclofenac 4′-hydroxylation and fluvastatin degradation with IC50 of 2.23 and 48.04 μM, respectively. Brewed green tea used in the clinical study also dose-dependently inhibited the metabolism of diclofenac and fluvastatin in vitro. However, no significant effects of GTE and brewed green tea were observed in plasma concentrations of fluvastatin. The geometric mean ratios with 90% CI for area under the plasma concentration–time curve (AUC0–∞) of fluvastatin were 0.993 (0.963–1.024, vs. brewed green tea) and 0.977 (0.935–1.020, vs. GTE).

Conclusions

Although in vitro studies indicated that EGCG and brewed green tea produce significant inhibitory effects on CYP2C9 activity, the concomitant administration of green tea and fluvastatin in healthy volunteers did not influence the pharmacokinetics of fluvastatin.

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Acknowledgements

We thank Dr. Yoshinori Tanino, Dr. Xintao Wang, Ms. Ayaka Ushigome, and Mr. Rintaro Miyo for their excellent technical support. This work was supported partly by the Honjo International Scholarship Foundation.

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Authors and Affiliations

  1. Department of Pharmacology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 9601295, Japan

    Shingen Misaka, Osamu Abe, Tomoyuki Ono, Yayoi Shikama & Junko Kimura

  2. Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan

    Osamu Abe & Hirooki Yabe

  3. Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

    Hideyuki Sato & Satomi Onoue

  4. Center for Medical Education and Career Development, Fukushima Medical University School of Medicine, Fukushima, Japan

    Yayoi Shikama

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  1. Shingen Misaka
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  2. Osamu Abe
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  3. Hideyuki Sato
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  4. Tomoyuki Ono
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Contributions

Misaka, Abe, Shikama, Onoue, Yabe, and Kimura participated in the research design. Misaka, Abe, Sato, and Ono conducted the experiments and clinical study. Misaka, Abe, Sato, Onoue, and Kimura performed the data analysis. Misaka, Abe, Shikama, Onoue, Yabe, and Kimura wrote or contributed to the writing of the manuscript.

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Correspondence to Shingen Misaka.

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The authors declared that they have no conflicts of interest.

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Misaka, S., Abe, O., Sato, H. et al. Lack of pharmacokinetic interaction between fluvastatin and green tea in healthy volunteers. Eur J Clin Pharmacol 74, 601–609 (2018). https://doi.org/10.1007/s00228-018-2420-x

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