In 1973,
Hans Nieper reported that lithium orotate contained 3.83 mg of elemental lithium per 100 mg and lithium carbonate contained 18.8 mg of elemental lithium per 100 mg. Nieper went on to claim that lithium did not dissolve from the orotate carrier until it passed through the
blood–brain barrier; however, a 1976 study documented that lithium concentrations within the brains of
rats were not statistically different between equivalent dosages of lithium from lithium orotate, lithium carbonate, or
lithium chloride. However, another study in 1978 study showed that eight hours after
intraperitoneal injections brain lithium concentrations of rats were significantly greater after lithium orotate than after lithium carbonate. While little
serum lithium remained at 24 h after injection of 2·0 m equiv kg−1 lithium carbonate, two‐thirds of the 2 h serum lithium concentration was present 24 h after lithium orotate. Furthermore, the 24 h brain concentration of lithium after lithium orotate was approximately three times greater than that after lithium carbonate. These data suggest the possibility that lower doses of lithium orotate than lithium carbonate may achieve therapeutic brain lithium concentrations and relatively stable serum concentrations. A year later, Smith and Schou repeated the experiment at a higher dose (2 mM Li+) and found that the higher concentrations in the brain could be possibly accounted for by
decreased renal function in rats treated with lithium orotate. The pharmacokinetics of lithium orotate in human brains is poorly documented, and there is no known mechanism by which orotate ions could alter the
pharmacokinetics of dissociated lithium ions, however, lithium intake appears to be effective even at low doses, and this may account for lithium orotate's claimed effectiveness. The reason why lithium orotate is poorly studied as a medication compared to lithium carbonate is concerns raised in 1979 regarding the potential amplified
renal toxicity of lithium orotate in comparison to lithium carbonate. ==Safety==