Animal studies have shown adverse effects on the fetus and fertility overall Label. There is conflicting evidence regarding the incidence of cardiovascular abnormalities in first trimester administration of lithium Label. However, studies in rats and mice have shown repeated daily dosing of lithium carbonate result in adverse effects on male reproductive organs, spermatogenesis, and testosterone levels Label. There is insufficient data regarding the carcinogenicity, mutagenicity, or fertility impairment of lithium carbonate Label. In rats, the oral LD50 is 525mg/kg and the inhalation LC50 is >2.17mg/L over 4 hours MSDS. ClearanceĬlearance is generally between 10 and 40mL/min but may be as low as 15mL/min in elderly patients and those with renal impairment 2. Other sources say it may be 7 to 20 hours 7. The half life of lithium carbonate is 18 to 36 hours Label. Lithium is primarily eliminated through the kidneys and elimination in the feces is insignificant Label.
Lithium carbonate is not metabolized before excretion Label. Lithium carbonate is not significantly protein bound Label 2. Volume of distributionĪpparent volume of distribution is 0.7 to 1.0L/kg Label 7. Lithium absorption is rapid and oral bioavailability is close to 100% 2.
Lithium can also inhibit GSK-3 through interfering with the magnesium ion in the active site 3. Lithium regulates phosphorylation of GSK-3 which regulates other enzymes through phosphorylation 3. This inhibition is thought to have multiple downstream effects that have yet to be clarified 3. Lithium acts on inositol polyphosphatase as an uncompetitive inhibitor 3.
However, stronger inhibitors of inositol monophosphatase are not as clinically effective and low levels of inositol triphosphate are associated with memory impairment 3, 6.
This inhibition lowers levels of inositol triphosphate 6. The “Inositol depletion theory” suggests lithium behaves as an uncompetitive inhibitor of inositol monophosphatase in a manner inversely proportional to the degree of stimulus 3. These targets are inositol monophosphatase, inositol polyphosphatase, and glycogen synthase kinase 3(GSK-3) 3, 6. However, the “inositol depletion theory” suggests 3 main potential targets 3. Lithium's mechanism of action is still unknown Label. Lithium's therapeutic action may be due to a number of effects, ranging from inhibition of enzymes such as glycogen synthase kinase 3, inositol phosphatases, or modulation of glutamate receptors 3, 4.
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