title: Time course of in vivo 5-HTT transporter occupancy by fluvoxamine.
abstract: The pharmacokinetics of drugs with specific binding sites in the brain needs to be evaluated at these sites. In this study, we measured the time course of the selective serotonin reuptake inhibitor fluvoxamine in the human brain based on serotonin transporter (5-HTT) occupancy by positron emission tomography. Consecutive positron emission tomography scans were performed using [11C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile before, 5 hours, 26 hours, and 53 hours after 50 mg of fluvoxamine administration in 6 healthy male volunteers (mean, 24.3 +/- 4.8 years). Quantification was performed using the multilinear reference tissue model 2. Mean 5-HTT occupancies were 72.9% +/- 4.9% at 5 hours, 50.3% +/- 11.0% at 26 hours, and 24.7% +/- 15.3% at 53 hours, and plasma concentrations were 13.9 +/- 5.5 ng/mL at 5 hours, 5.1 +/- 3.2 ng/mL at 26 hours, and 1.5 +/- 1.7 ng/mL at 53 hours. The relationship between the plasma concentration of fluvoxamine and 5-HTT occupancy at these different time points was fitted to the law of mass action.
authors.affiliation: Brain Imaging Project, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ichimiya
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Yasuno
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000814:Aniline Compounds; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D016666:Fluvoxamine / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D015203:Reproducibility of Results; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013440:Sulfides
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D018687:Antidepressive Agents, Second-Generation; D002250:Carbon Radioisotopes; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; D016666:Fluvoxamine