title: A positron emission tomography microdosing study with sertraline in healthy volunteers.
abstract: OBJECTIVE
  This study explored microdosing methods for evaluating the distribution and pharmacokinetics (PK) of a central nervous system (CNS) drug candidate.
  
  
  METHODS
  We used sertraline as a model drug. In this open-label, one-arm, three-period, multiple-dosing study, 10 healthy male volunteers received 6-day administrations of sertraline at doses of 5, 25 or 50 mg/d in three different periods. Before the first dose of Period 1, and 24 h after the last dose of each period, an intravenous bolus of [11C]sertraline was injected for positron emission tomography (PET) scanning. After the sixth dose in each period, serial blood samples were collected at scheduled intervals over 48 h; then serum sertraline concentrations were determined with liquid chromatography-tandem mass spectrometry (LC-MS/MS).
  
  
  RESULTS
  Sertraline was distributed in the brain within 20 min, and it was highly distributed in the putamen, cingulate, and thalamus. Linearity in steady-state Cmax and AUClast were observed in the 5 - 50 mg dose range. The results suggested that microdosing with PET was a useful method for exploring the bloodbrain- barrier penetration and distribution of a candidate CNS drug.
  
  
  CONCLUSIONS
  This study described a microdosing method that combined PET with LC-MS/MS for determining the brain distribution and PK characteristics of a CNS drug candidate.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Shin
authors.forename: Kyu-Pyo
authors.initials: KP
authors.lastname: Kim
authors.forename: Kyoung Soo
authors.initials: KS
authors.lastname: Lim
authors.forename: Ji Who
authors.initials: JW
authors.lastname: Kim
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Bo Yeun
authors.initials: BY
authors.lastname: Yang
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Lee
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Jung
authors.forename: Seo-Hyun
authors.initials: SH
authors.lastname: Yoon
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
mesh_terms: D000328:Adult; D002250:Carbon Radioisotopes; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics*; D020280:Sertraline / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D002250:Carbon Radioisotopes; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline