Stable isotopes of lithium: in vivo differential distribution between plasma and cerebrospinal fluid

Area of Science:

• Pharmacokinetics
• Isotope research
• Biomedical science

Background:

• Stable isotopes are typically assumed to behave identically in biological systems.
• Previous research indicated differential uptake of lithium isotopes by red blood cells.
• The in vivo behavior and pharmacokinetic differences between lithium isotopes were not well-established.

Purpose of the Study:

• To investigate the in vivo pharmacokinetics of stable lithium isotopes (6Li and 7Li) in adult cats.
• To compare the plasma concentration, distribution, and elimination rates of 6Li and 7Li.
• To assess the transport of lithium isotopes across the blood-brain barrier.

Main Methods:

• Administered single doses of 6LiCl or 7LiCl to adult cats via gastric intubation.
• Collected plasma samples over time to determine lithium isotope concentrations.
• Collected simultaneous cerebrospinal fluid (CSF) and plasma samples to evaluate isotope distribution across the blood-brain barrier.

Main Results:

• The average plasma concentration of 6Li was higher than 7Li between 2 and 9 hours post-administration.
• 6Li exhibited a shorter elimination half-life in the slow elimination phase (12.9 hours) compared to 7Li (15.9 hours).
• The CSF/plasma ratio for 6Li was higher than for 7Li 2-6 hours after administration, indicating differential transport across the blood-brain barrier.

Conclusions:

• The acute pharmacokinetics of 6Li and 7Li differ in terms of plasma disappearance rate and compartmental distribution.
• Factors beyond simple concentration gradients influence lithium isotope transport across the blood-brain barrier.
• These findings suggest a potential for differential therapeutic or toxic effects of 6Li and 7Li in clinical applications, such as treating manic-depressive illness.