title: Determination of radioactivity in infant, juvenile and adult rat brains after injection of anti-influenza drug [¹¹C]oseltamivir using PET and autoradiography.
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 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 [(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.
authors: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, Japan.
authors: Akiko
authors: A
authors: Hatori
authors: Joji
authors: J
authors: Yui
authors: Kazuhiko
authors: K
authors: Yanamoto
authors: Tomoteru
authors: T
authors: Yamasaki
authors: Kazunori
authors: K
authors: Kawamura
authors: Makoto
authors: M
authors: Takei
authors: Takuya
authors: T
authors: Arai
authors: Toshimitsu
authors: T
authors: Fukumura
authors: Ming-Rong
authors: MR
authors: Zhang
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000254:growth & development*; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D053139:Oseltamivir / Q000097:blood / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D002247:Carbon Isotopes; D053139:Oseltamivir