Determination of radioactivity in infant, juvenile and adult rat brains after injection of anti-influenza drug [11C]oseltamivir using PET and autoradiography
Determination of radioactivity in infant, juvenile and adult rat brains after injection of anti-influenza drug [11C]oseltamivir using PET and autoradiography
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DOI：
10.1016/j.neulet.2011.03.055
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发表时间：
2011-05-20
影响因子：
2.5
通讯作者：
Zhang, Ming-Rong
中科院分区：
文献类型：
--
作者：
Hatori, Akiko;Yui, Joji;Zhang, Ming-Rong
磷酸奥司他韦（Tamiflu (R)）是一种口服活性抗流感药物，经水解生成其代谢产物Ro 64-0802，具有抑制流感病毒的强效活性。与使用奥司他韦有关的年轻流感患者的异常行为在经常开达菲的国家已发展成为一个社会问题。确定大脑中奥司他韦的量并阐明其存在与神经精神副作用之间的关系是很重要的。本研究的目的是利用PET和放射自显影技术测定大鼠注射[C-11]奥司他韦后，幼鼠、幼鼠和成年大鼠脑内的放射性。注射该放射性配体后，婴儿脑部的放射性最高，随年龄增长而降低。婴儿大脑的离体放射自显像显示，小脑的放射性相对高于大脑。环孢素A （p -糖蛋白抑制剂）预处理可增加脑放射性。这些结果为阐明为什么奥司他韦的神经精神副作用发生在年轻患者中提供了有益的见解。2011爱思唯尔爱尔兰有限公司版权所有。
Oseltamivir phosphate (Tamiflu (R)) is an orally active anti-influenza drug, which is hydrolyzed to its metabolite Ro 64-0802 inhibiting the influenza virus with potent activity. The abnormal behavior of young influenza patients associated with the use of oseltamivir has developed to a social problem in countries where Tamiflu is often prescribed. It is important to determine the amount of oseltamivir in the brain and to elucidate the relationship between its presence and neuropsychiatric side effects. The aim of this study was to determine the radioactivity in the infant, juvenile and adult rat brains after injection of [C-11]oseltamivir into the rats using PET and autoradiography. After injection of this radioligand, the highest radioactivity was found in the infant brain and the radioactivity level decreased with age. Ex vivo autoradiography on the infant brain displayed a relatively higher radioactivity in the cerebellum than that in the cerebrum. Pretreatment with cyclosporin A (an inhibitor for P-glycoprotein) increased the brain radioactivity. These results give helpful insights into elucidating why the neuropsychiatric side effects of oseltamivir occur in young patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved.