24-hour lithium concentration in human brain studied by Li-7 magnetic resonance spectroscopy

Area of Science:

• Neuroscience
• Pharmacology
• Biomedical Imaging

Background:

• Lithium is a common mood stabilizer for bipolar disorder.
• Understanding brain lithium pharmacokinetics is essential for optimizing therapeutic efficacy and minimizing toxicity.
• Previous studies have primarily focused on serum lithium levels, with limited data on brain concentrations over time.

Purpose of the Study:

• To investigate the dynamic changes in brain and serum lithium concentrations over a 48-hour period.
• To determine the relationship between brain and serum lithium levels and their respective half-lives.
• To establish the implications of these findings for standardized lithium monitoring using magnetic resonance spectroscopy (MRS).

Main Methods:

• Two subjects in steady-state lithium treatment received lithium carbonate orally once daily.
• Brain and serum lithium concentrations were measured every 2 hours for 24 hours, and again at 48 hours post-intake.
• Brain lithium was quantified using 7Li magnetic resonance spectroscopy (MRS).

Main Results:

• Brain lithium concentrations exhibited a peak-trough pattern that followed serum lithium levels, albeit attenuated.
• The brain-to-serum lithium concentration ratio varied significantly (0.5–1.3) but was independent of serum lithium concentration.
• Median half-life was longer in the brain (28 hours) than in serum (16 hours).
• Morning brain lithium levels were approximately 75% of the standard 12-hour serum concentration.

Conclusions:

• Brain lithium levels fluctuate rhythmically over a 24-hour period following oral intake.
• MRS measurements of brain lithium require standardized conditions, including fixed intervals post-intake and consistent treatment regimens, for reliable comparisons.
• These findings highlight the importance of considering brain lithium dynamics for therapeutic drug monitoring.