Pharmacokinetics of lithium in the elderly

The disposition and elimination of lithium was examined in nine female geriatric patients (aged 67 to 80 years) maintained on lithium carbonate as a once daily dose (300 to 600 mg) for the treatment of recurrent depression. Following the morning lithium dose (0.21 +/- 0.06 mmol/kg/day, mean +/- standard deviation), a peak steady state serum concentration of 0.83 +/- 0.25 mmol/liter was achieved at 2.2 +/- 1.2 hours. The mean distribution half-life (alpha-t1/2) was 2.7 +/- 1.2 hours, with distribution being complete at 10.6 +/- 3.0 hours. The mean terminal elimination half-life (beta-t1/2), the mean apparent oral clearance (Cl), and the mean apparent volume of distribution (Varea) were 26.9 +/- 5.5 hours, 15.6 +/- 4.0 ml/min, and 0.64 +/- 0.16 liter/kg, respectively. Compared to a younger adult cohort (35 +/- 10 years), the lithium Cl and Varea were significantly reduced and the alpha- but not beta-t1/2 prolonged in the elderly (p less than 0.05). Based on these pharmacokinetic differences, geriatric patients may require one-third to one-half less lithium than younger adults. The 12-hour standard serum lithium concentration remained a value of minimal intersubject variability when lithium was administered once daily. However, the therapeutic concentration range based on this 12-hour standard serum lithium concentration needs to be redefined for the prophylaxis of unipolar disorders in the elderly.