Abstract Title:

Determination of radioactivity in infant, juvenile and adult rat brains after injection of anti-influenza drug [¹¹C]oseltamivir using PET and autoradiography.

Abstract Source:

Neurosci Lett. 2011 May 20 ;495(3):187-91. Epub 2011 Apr 2. PMID: 21443926

Abstract Author(s):

Akiko Hatori, Joji Yui, Kazuhiko Yanamoto, Tomoteru Yamasaki, Kazunori Kawamura, Makoto Takei, Takuya Arai, Toshimitsu Fukumura, Ming-Rong Zhang

Article Affiliation:

Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, Japan.

Abstract:

Oseltamivir phosphate (Tamiflu(®)) 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 isoften 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 [(11)C]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.

Study Type : Animal Study

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