@article{oai:repo.qst.go.jp:00048726,
 author = {Moriguchi, Sho and Takano, Harumasa and Kimura, Yasuyuki and Nagashima, Tomohisa and Takahata, Keisuke and Kubota, Manabu and Kitamura, Soichiro and Ishii, Tatsuya and Ichise, Masanori and Zhang, Ming-Rong and Shimada, Hitoshi and Mimura, Masaru and H., Meyer Jeffrey and Higuchi, Makoto and Suhara, Tetsuya and 森口 翔 and 高野 晴成 and 木村 泰之 and 永嶌 朋久 and 高畑 圭輔 and 久保田 学 and 北村 聡一郎 and 石井 辰弥 and 市瀬 正則 and 張 明栄 and 島田 斉 and 三村 將 and 樋口 真人 and 須原 哲也},
 issue = {12},
 journal = {The International Journal of Neuropsychopharmacology},
 month = {Jul},
 note = {Background: The norepinephrine transporter (NET) in the brain has been targeted in the treatment of psychiatric disorders. Duloxetine is a serotonin and norepinephrine reuptake inhibitor that has been widely used for the treatment of depression. However, the relationship between dose and plasma concentration of duloxetine and NET occupancy in the human brain has not been determined. In this study, we examined NET occupancy by different doses of duloxetine.
Methods: We calculated NET occupancies from two positron emission tomography (PET) scans using (S,S)-[18F]FMeNER-D2 before and after a single oral dose of duloxetine (20 mg, n = 3; 40 mg, n = 3; 60 mg, n = 2). PET scans were performed from 120 to 180 min after an intravenous bolus injection of (S,S)-[18F]FMeNER-D2. Venous blood samples were taken to measure the plasma concentration of duloxetine just before and after the second PET scan.
Results: NET occupancy by duloxetine was 29.7% at 20 mg, 30.5% at 40 mg, and 40.0% at 60 mg. The estimated dose of duloxetine inducing 50% NET occupancy (ED50) was 76.8 mg, and the estimated plasma drug concentration inducing 50% NET occupancy (EC50) was 58.0 ng/mL.
Conclusions: NET occupancy by clinical doses of duloxetine was approximately 30–40% in human brain as estimated using PET with (S,S)-[18F]FMeNER-D2.},
 pages = {957--962},
 title = {Occupancy of norepinephrine transporter by duloxetine in human brains measured by positron emission tomography with (S,S)-[18F]FMeNER-D2},
 volume = {20},
 year = {2017}
}