Journal Article Occupancy of norepinephrine transporter by duloxetine in human brains measured by positron emission tomography with (S,S)-[18F]FMeNER-D2

Moriguchi, Sho  ,  Takano, Harumasa  ,  Kimura, Yasuyuki  ,  Nagashima, Tomohisa  ,  Takahata, Keisuke  ,  Kubota, Manabu  ,  Kitamura, Soichiro  ,  Ishii, Tatsuya  ,  Ichise, Masanori  ,  Ming-Rong, Zhang  ,  Shimada, Hitoshi  ,  Mimura, Masaru  ,  H. Meyer, Jeffrey  ,  Higuchi, Makoto  ,  Suhara, Tetsuya

20 ( 12 )  , pp.957 - 962 , 2017-07 , Oxford University Press
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.

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