Toxicity And Pharmacokinetics Of Lithium Ascorbate

Lithium salts are established pharmacological agents in psychiatry, but their clinical use is limited by concerns about toxicity, narrow therapeutic range, and the need for blood-level monitoring. Lithium ascorbate, an organic lithium salt, has been proposed as a potentially lower-toxicity lithium-containing compound, but its toxicological and pharmacokinetic profile requires systematic evaluation. This study assessed the toxicity and pharmacokinetics of lithium ascorbate in rabbits, mice, and rats using repeated-dose, acute-dose, cumulative-toxicity, and tissue-distribution experiments. In rabbits, repeated intragastric administration at doses up to 150 mg/kg for 180 days produced no signs of chronic systemic toxicity or local irritation. In acute intragastric studies, toxicity occurred only at high doses, with LD50 values of 6140 mg/kg in male mice, 6920 mg/kg in female mice, 4810 mg/kg in male rats, and 5070 mg/kg in female rats. Acute intravenous administration in rats caused no mortality up to 3000 mg/kg, while higher doses produced systemic toxicity and dose-associated local vascular injury. Repeated escalating intragastric dosing in male rats showed moderate cumulative toxicity, with a cumulation coefficient of 3.74. Pharmacokinetic analysis after intragastric administration showed rapid absorption, broad tissue distribution, and prolonged lithium retention in blood and frontal brain tissue. Overall, lithium ascorbate demonstrated low-to-moderate preclinical toxicity, supporting further comparative, mechanistic, and translational safety studies before conclusions about human dosing or clinical safety can be made.