, Volume 185, Issue 3, pp 395–399 | Cite as

A dose-finding study of duloxetine based on serotonin transporter occupancy

  • Akihiro Takano
  • Kazutoshi Suzuki
  • Jun Kosaka
  • Miho Ota
  • Shoko Nozaki
  • Yoko Ikoma
  • Shuji Tanada
  • Tetsuya Suhara
Original Investigation



Positron emission tomography (PET) has been utilized for determining the dosage of antipsychotic drugs. To evaluate the dosage of antidepressants such as selective serotonin reuptake inhibitors, serotonin transporter occupancy (5-HTT) is also a useful index.


We investigated the degree of 5-HTT occupancy with different doses of the antidepressant duloxetine and the time-course of 5-HTT occupancy using PET.


PET scans with [11C]DASB were performed before and after a single administration of duloxetine (5–60 mg), and three consecutive scans were performed after a single dose or repeated doses of 60 mg of duloxetine.


5-HTT occupancies by duloxetine were increased by 35.3 to 86.5% with dose and plasma concentration increments. The ED50 value of 5-HTT occupancy was 7.9 mg for dose and 3.7 ng/ml for plasma concentration. In the time-course of 5-HTT occupancy, mean occupancies were 81.8% at 6 h, 71.9% at 25 h, and 44.9% at 53 h after a single administration, and 84.3% at 6 h, 71.9% at 49 h, and 47.1% at 78 h after repeated administrations.


Based on 5-HTT occupancy, 40 mg and more of duloxetine was needed to attain 80% occupancy, and 60 mg of duloxetine could maintain a high level of 5-HTT occupancy with a once-a-day administration schedule.


Duloxetine Occupancy 5-HTT PET DASB Time-course 



This research was conducted as LY248686 (duloxetine) phase I study in Japan, and was partially supported by Shionogi and Co., Ltd.


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Akihiro Takano
    • 1
  • Kazutoshi Suzuki
    • 1
  • Jun Kosaka
    • 1
  • Miho Ota
    • 1
  • Shoko Nozaki
    • 1
  • Yoko Ikoma
    • 1
  • Shuji Tanada
    • 2
  • Tetsuya Suhara
    • 1
  1. 1.Molecular Imaging CenterNational Institute of Radiological SciencesChibaJapan
  2. 2.Department of Medical ImagingNational Institute of Radiological SciencesChibaJapan

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