J Clin Pharmacol
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Citing Articles
Right arrow Citing Articles via ISI Web of Science (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Uchida, S.
Right arrow Articles by Yamada, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Uchida, S.
Right arrow Articles by Yamada, S.

DRUG INTERACTIONS

Effects of Ginkgo Biloba Extract on Pharmacokinetics and Pharmacodynamics of Tolbutamide and Midazolam in Healthy Volunteers

Shinya Uchida, PhD, Hiroshi Yamada, MD, PhD, Xiao Dong Li, MD, PhD, Shuji Maruyama, MS, Yuki Ohmori, PhD, Tomomi Oki, PhD, Hiroshi Watanabe, MD, PhD, Keizo Umegaki, PhD, Kyoichi Ohashi, MD, PhD and Shizuo Yamada, PhD

From the Departments of Pharmacokinetics and Pharmacodynamics, Center of Excellence Program in the 21st Century (Dr Uchida, Ms Maruyama, Dr Ohmori, Dr Oki, Dr S. Yamada) and Division of Drug Evaluation and Informatics (Dr H. Yamada), School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan; Department of Clinical Pharmacology & Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan (Dr Li, Dr Watanabe); National Institute of Health and Nutrition, Tokyo, Japan (Dr Umegaki); and Department of Clinical Pharmacology & Therapeutics, School of Medicine, Oita University, Oita, Japan (Dr Ohashi).

This study was undertaken to clarify the influence of repeated oral administration of Ginkgo biloba extract (GBE) on CYP2C9 and CYP3A4. CYP2C9 probe (tolbutamide, 125 mg) and CYP3A4 probe (midazolam, 8 mg) were orally administered to 10 male healthy volunteers before and after GBE intake (360 mg/d) for 28 days, and they received 75 g glucose after the dosing of tolbutamide. Plasma drug concentrations and blood glucose levels were measured. The area under concentration versus time curve (AUC0-{infty}) for tolbutamide after GBE intake was slightly but significantly (16%) lower than that before GBE intake. Concomitantly, GBE tended to attenuate AUC0-2 of blood glucose-lowering effect of tolbutamide. AUC0-{infty} for midazolam was significantly (25%) increased by GBE intake and oral clearance was significantly (26%) decreased. Thus, it is suggested that the combination of GBE and drugs should be cautious in terms of the potential interactions, especially in elderly patients or patients treated with drugs exerting relatively narrow therapeutic windows.

Key Words: Ginkgo biloba extract • CYP2C9 • CYP3A4 • pharmacokinetic interaction

Address for reprints: Shizuo Yamada, PhD, Departments of Pharmacokinetics and Pharmacodynamics and Center of Excellence Program in the 21st Century, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526; e-mail: yamada{at}ys7.u-shizuoka-ken.ac.jp.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American College of Clinical Pharmacology