title: A dose-finding study of duloxetine based on serotonin transporter occupancy.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 9-1, Anagawa 4-Chome, Inage-ku, Chiba, 263-8555, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takano
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Jun
authors.initials: J
authors.lastname: Kosaka
authors.forename: Miho
authors.initials: M
authors.lastname: Ota
authors.forename: Shoko
authors.initials: S
authors.lastname: Nozaki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikoma
authors.forename: Shuji
authors.initials: S
authors.lastname: Tanada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000097:blood; D013876:Thiophenes / Q000008:administration & dosage* / Q000097:blood
chemical_list: D000068736:Duloxetine Hydrochloride; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes