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Human brain fluoxetine concentrations

C N Karson1, J E Newton, R Livingston

  • 1Department of Psychiatry and Behavioral Sciences, University of Arkansas for Medical Sciences, Little Rock.

The Journal of Neuropsychiatry and Clinical Neurosciences
|January 1, 1993
PubMed
Summary
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Magnetic resonance spectroscopy (MRS) can measure in vivo brain concentrations of fluoxetine and its metabolite. Fluoxetine accumulates significantly in the brain compared to plasma, reaching a potential plateau after 6-8 months of treatment.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Medical Imaging

Background:

  • Fluoxetine is a widely prescribed antidepressant.
  • Measuring drug concentrations in the brain non-invasively is challenging.
  • Understanding drug distribution is crucial for optimizing treatment.

Purpose of the Study:

  • To evaluate the utility of fluorine-19 magnetic resonance spectroscopy (MRS) for quantifying in vivo brain concentrations of fluoxetine and its active metabolite, norfluoxetine.
  • To determine the brain-to-plasma ratio of fluoxetine/norfluoxetine.
  • To investigate the time course of brain drug accumulation.

Main Methods:

  • Utilized fluorine-19 magnetic resonance spectroscopy (MRS) in 22 subjects undergoing fluoxetine treatment.
  • Measured in vivo brain concentrations of fluoxetine and norfluoxetine.

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  • Compared brain concentrations with simultaneously measured plasma concentrations.

    • Main Results:

    • Fluoxetine/norfluoxetine was successfully measured in the human brain using 19F-MRS.
    • Brain concentrations of fluoxetine/norfluoxetine ranged up to 10.7 µg/ml.
    • The apparent brain-to-plasma concentration ratio was approximately 20:1.
    • Brain concentrations appeared to plateau between 6 and 8 months of treatment.

    Conclusions:

    • Fluorine-19 MRS is a viable method for measuring in vivo brain concentrations of fluoxetine/norfluoxetine.
    • Fluoxetine demonstrates significant accumulation in the human brain relative to plasma.
    • Findings align with animal study data on brain antidepressant concentrations.