Plasma and brain pharmacokinetics of previously unexplored lithium salts

摘要

Despite its narrow therapeutic window, lithium is regarded as the gold standard comparator and benchmark treatment for mania. Attempts to find new drugs with similar therapeutic activities have yielded new chemical entities. However, these new drugs have yet to match the many bioactivities attributable to lithium's efficacy for the treatment of neuropsychiatric diseases. Consequently, an intense effort for re-engineering lithium therapeutics using crystal engineering is underway. The evaluation of pharmacokinetics of previously unexplored lithium salts with organic anions (i.e. lithium salicylate) has found that these lithium salts exhibit profoundly different pharmacokinetics compared to the more common FDA approved salt, lithium carbonate, in rats. Remarkably, lithium salicylate produced elevated blood and brain levels of lithium beyond 48 hours post-dose without the sharp peak that contributes to the toxicity problems of current lithium therapeutics.