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19F magnetic resonance spectroscopy investigation in vivo of acute and steady-state brain fluvoxamine levels in obsessive-compulsive disorder
Am J Psychiatry 1997;154:516-522.
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OBJECTIVE: The purpose of this study was to investigate the pharmacokinetics of fluvoxamine in the human brain by using fluorine-19 magnetic resonance spectroscopy (19F MRS) and to assess the relationships among fluvoxamine brain levels, fluvoxamine plasma levels, and clinical efficacy. METHOD: Eight subjects with DSM-IV obsessive-compulsive disorder were entered into a prospective, open- label treatment trial of fluvoxamine. 19F MRS measurements of whole brain drug and metabolite concentrations and spin-lattice (T1) relaxation times were performed serially in seven subjects for up to 5 months. A psychiatric determination of clinical response and a blood sample for plasma fluvoxamine measurement were obtained at each 19F MRS session. RESULTS: The subjects achieved steady-state brain concentrations of fluvoxamine within 30 days after consistent daily dosing, as determined by stabilization of brain fluvoxamine concentrations. The mean brain-to-plasma ratio at steady state was 24 to 1. Brain fluvoxamine T1 values from 140 to 230 msec were observed. All but one subject experienced substantial improvement in symptoms. The one nonresponder exhibited several-fold higher plasma and brain fluvoxamine levels. CONCLUSIONS: Brain fluvoxamine levels were substantially higher than plasma levels. Steady-state brain levels correlated to plasma levels but not to dose. Systematic assessment of treatment response in relation to brain or plasma fluvoxamine level was not feasible because of the marked and rapid clinical response during open-label treatment. These data suggest that fluvoxamine attains brain steady-state levels substantially faster than fluoxetine, with corresponding clinical implications.

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