THE PHARMACOKINETICS OF LITHIUM IN THE BRAIN, CEREBROSPINAL FLUID AND SERUM OF THE RAT

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Abstract
Addition of lithium carbonate (55 mmol/kg dry wt.) to the diet of rats for 4 days resulted in ratios between lithium in the brain and serum and between the cerebrospinal fluid (CSF) and serum of approx. 1 and 0.4, respectively. The relationships between the concentrations were linear. After single intraperitoneal injections of lithium chloride (5 mmol/kg body wt.) the concentration of lithium in the CSF was greater than that of the brain for 2 h. Repeated subcutaneous injections of lithium chloride (0.9 mmol/kg body wt.) resulted in steady state ratios corresponding to those observed when lithium was given in the diet. The rate of elimination from the CSF was intermediate between that of the serum and cerebral tissue until a new equilibrium was reached after approx. 24 h. At that time the ratios between lithium in the brain and serum, and in the CSF and serum were increased to approx. 5 and 0.8, respectively. These results are consistent with passive transfer kinetics of lithium in the CSF and elimination of lithium from the cerebral tissue via the CSF. The results may explain some of the phenomena observed in patients during intoxication with lithium.