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.