Effects of continuous ingestion of green tea or grape seed extracts on the pharmacokinetics of midazolam.

Masataka Nishikawa, Noritaka Ariyoshi, Akira Kotani, Itsuko Ishii, Hiroyoshi Nakamura, Hiromitsu Nakasa, Mayuri Ida, Hideo Nakamura, Nobuhito Kimura, Maharu Kimura, Atsushi Hasegawa, Fumiyo Kusu, Shigeru Ohmori, Kazuyoshi Nakazawa, Mitsukazu Kitada

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59 Citations (Scopus)

Abstract

Limited systematic data on herb-drug interaction are available, despite many opportunities to concomitant use of herb with prescribed drugs. We investigated the effects of 15 herbal extracts in dietary supplements on CYP2C9, CYP2D6 and CYP3A4 activities in human liver microsomes. Strong inhibition of these CYP activities was found by the addition of green tea extracts (GTE) or grape seed extracts (GSE) in vitro. To examine the effects of these extracts on CYP3A activities in vivo, the pharmacokinetics of midazolam (MDZ) was analyzed in rats. Although single treatments with these extracts had negligible effects, 1 week of treatment with them resulted in a significant increase in the ke of intravenously administered MDZ, indicating the induction of CYP3A in the liver. In contrast, 1 week of treatment with GTE, but not GSE, caused a significant increase in the C(max) and AUC(0-infinity) of orally administered MDZ without change in the t(1/2), suggesting a reduction in CYP3A activity in the small intestines. These studies indicate that subchronic ingestion of GTE or GSE may alter the pharmacokinetics of MDZ, and the effects of GTE on CYP3A activity appear opposite between liver and small intestine, which could not be predicted from in vitro experiments.

Original languageEnglish
Pages (from-to)280-289
Number of pages10
JournalDrug Metabolism And Pharmacokinetics
Volume19
Issue number4
DOIs
Publication statusPublished - Aug 2004
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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    Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., & Kitada, M. (2004). Effects of continuous ingestion of green tea or grape seed extracts on the pharmacokinetics of midazolam. Drug Metabolism And Pharmacokinetics, 19(4), 280-289. https://doi.org/10.2133/dmpk.19.280