Lithium concentration in the muscle compartment of manic-depressive patients during lithium therapy

Pharmacokinetic (PK) techniques were used to study the effect of lithium (Li+) on Li+ fluxes and concentrations in body compartments of manic-depressives. Patients not yet on Li+ therapy were similar to normal controls in all parameters. Comparison of patients before and during chronic Li+ therapy showed no effect of Li+ therapy on intestinal absorption and renal excretion of Li+. The calculated erythrocyte (RBC)-to-plasma Li+ concentration ratio increased with Li+ therapy, as already known from direct measurements. The calculated muscle-to-plasma Li+ concentration ratio was 6-8 times higher than the RBC ratio, and increased from 1.8 to 4.2 with Li+ therapy. The higher Li+ concentration in human muscle compared to RBC is attributed to muscle's higher inside-negative resting potential, and may underlie side effects that arise in muscle from Li+ therapy. The discrepancy between the observed muscle-to-plasma ratio and that predicted for a passively distributed ion is attributed to extrusion by a countertransport process, and the increase in the observed ratio with Li+ therapy is attributed to inhibition of countertransport, as already established for RBC. Since muscle resembles nerve as an excitable cell, muscle Li+ warrants evaluation as a predictor of therapeutic response and side effects during Li+ therapy.