Lithium carbonate and granulocyte production: Dose optimization

To determine the optimal dose of lithium for inducing granulocytosis, the authors administered lithium carbonate to normal volunteers at five dose levels. The authors performed assessments of circulating and marginated blood pools of granulocytes and of marrow reserve granulocytes to confirm that the early granulocytosis following lithium administration is due to increased granulocyte production rather than redistribution. At 300 mg/day and 600 mg/day, lithium had no significant effect on granulocyte production. Doses of 900, 1200, and 1500 mg/day, corresponding to lithium levels of 0.55 to 1.50 mEq/liter, were associated with increased granulocyte production. Within this therapeutic range, no correlation between lithium level and granulocyte production was demonstrated. This study suggests that any lithium dose which achieves a lithium level of greater than 0.55 mEq/liter, i.e., doses greater than or equal to 900 mg/day, is adequate to induce granulocytosis. While lithium did not increase platelet production, doses of 900 mg/day to 1500 mg/day were associated with decreased bleeding times.