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eCAM Advance Access published online on November 1, 2009
eCAM, doi:10.1093/ecam/nep159
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© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Experimental Adjustment on Drug Interactions through Intestinal CYP3A Activity in Rat: Impacts of Kampo Medicines Repeat Administered

Natsumi Kinoshita1, Yuriko Yamaguchi1, Xiao-Long Hou1, Kyoko Takahashi2 and Koichi Takahashi1

1Department of Pharmaceutics, School of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, 2Department of Medicinal Resources, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

To provide the information that is necessary for making the proper use of kampo medicines, we have proposed the adequate methodology focused on the following issues: (i) kampo medicines emphasize the effects produced by the combination of herbal drugs rather than the individual effect of any single herb and (ii) Intestinal CYP3A has become a key factor for the bioavailability of orally administrated drugs. In the present study, we investigated both the in vivo and in vitro effects of Saireito and Hochuekkito (kampo formulas) on CYP3A activities. From our study, oral pre-treatment with Saireito or Hochuekkito did not affect the pharmacokinetics of nifedipine after intravenous administration to rats. When nifedipine was administered to rat intrajejunum, a significant decrease of AUC was showed by pre-treatment with both kampo formulas. Saireito pre-treatment led to 80% decrease in Cmax of nifedipine. Saireito caused significant increases in both protein expression and metabolic activity of CYP3A in intestinal microsome, whereas it had no effect on CYP3A in hepatic microsome. Our result also showed that this affect of Saireito can be gone by wash-out with 1 week. These findings demonstrated that Saireito may induce CYP3A activity of intestine but not of liver in rats. When resources for research are limited, well-designed scientific studies except clinical trials also have many advantages.

Keywords: CYP3A – drug interaction – intestinal metabolism – Kampo medicine – nifedipine

For reprints and all correspondence: Koichi Takahashi, Department of Pharmaceutics, School of Pharmaceutical Sciences, Mukogawa Women's University, 11-68, Koshien, Kyuban-cho, Nishinomiya 663-8179, Japan. Tel: +81 798 45 9943; Fax: +81 798 41 2792; E-mail: koichi{at}mukogawa-u.ac.jp

Received August 26, 2008; accepted September 15, 2009


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