Kubota Yoko, Kobayashi Kyoko, Tanaka Naoko, Nakamura Kazuki, Kunitomo Masaru, Umegaki Keizo, Shinozuka Kazumasa
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
J Pharm Pharmacol. 2004 Mar;56(3):401-5. doi: 10.1211/0022357022836.
In a previous study, we found that orally administered Ginkgo biloba extract (GBE) induced hepatic cytochrome P450 (CYP) in rats, especially the CYP2B type. This fact suggested that GBE influenced the availability and safety of drugs that were metabolized via CYP2B type enzymes. To confirm this possibility, in this study we examined the effect of feeding a 0.1, 0.5 and 1.0% GBE diet for 2 weeks on the pharmacokinetics and pharmacological action of phenobarbital, which is known to be metabolized by CYP2B in Wistar rats. The feeding of GBE markedly shortened the sleeping time in rats. Furthermore, the maximal phenobarbital plasma concentration (Cmax) and the 24-h area under the curve (AUC0-24) were decreased in rats fed GBE. These findings indicate that GBE reduces the therapeutic potency of phenobarbital via enhancement of cytochrome P450 expression, and raises the possibility that GBE and drug interactions may occur clinically.
在之前的一项研究中，我们发现给大鼠口服银杏叶提取物（GBE）可诱导其肝脏细胞色素P450（CYP），尤其是CYP2B类型。这一事实表明GBE会影响通过CYP2B型酶代谢的药物的有效性和安全性。为证实这种可能性，在本研究中，我们研究了给Wistar大鼠喂食0.1%、0.5%和1.0%的GBE饮食2周对苯巴比妥药代动力学和药理作用的影响，已知苯巴比妥在Wistar大鼠中由CYP2B代谢。喂食GBE显著缩短了大鼠的睡眠时间。此外，喂食GBE的大鼠中苯巴比妥的最大血浆浓度（Cmax）和24小时曲线下面积（AUC0-24）降低。这些发现表明GBE通过增强细胞色素P450表达降低了苯巴比妥的治疗效力，并增加了GBE与药物在临床上可能发生相互作用的可能性。
