European Journal of Clinical Pharmacology

, Volume 74, Issue 5, pp 601–609 | Cite as

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

  • Shingen Misaka
  • Osamu Abe
  • Hideyuki Sato
  • Tomoyuki Ono
  • Yayoi Shikama
  • Satomi Onoue
  • Hirooki Yabe
  • Junko Kimura
Pharmacokinetics and Disposition



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.


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.


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).


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.


CYP2C9 Diclofenac (−)-Epigallocatechin gallate Fluvastatin Green tea Pharmacokinetics 



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.

Author contribution

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.

Compliance with ethical standards

Competing interests

The authors declared that they have no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PharmacologyFukushima Medical University School of MedicineFukushimaJapan
  2. 2.Department of NeuropsychiatryFukushima Medical University School of MedicineFukushimaJapan
  3. 3.Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical SciencesUniversity of ShizuokaShizuokaJapan
  4. 4.Center for Medical Education and Career DevelopmentFukushima Medical University School of MedicineFukushimaJapan

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