1. The possible natriuretic and kaliuretic effects of a single dose of lithium, as used in lithium clearance studies, were investigated in 15 healthy subjects on fixed sodium (100 mmol/24 h) and potassium (70 mmol/24 h) intakes. Lithium carbonate (300 mg or 600 mg) or placebo tablets were administered, double-blind and in random order, midway through a 48 h urine collection (divided into six 8 h periods), at 23.00 hours.
2. During the three 24 h periods which preceded the administration of lithium or placebo (control days), rates of sodium and potassium excretion followed normal circadian patterns, but no differences in excretion rates between the 3 control days were observed. Placebo tablets did not affect excretion rates.
3. After the 300 mg dose of lithium carbonate, 24 h sodium excretion increased by approximately 17 mmol (P < 0.05); almost all of the natriuretic effect occurred during the first two 8 h periods. No effect on potassium excretion was observed.
4. After the 600 mg dose of lithium carbonate, 24 h sodium excretion increased by approximately 48 mmol (P < 0.001) and 24 h potassium excretion increased by approximately 19 mmol (P < 0.01). These effects were confined to the first two 8 h periods and thus occurred before and during the usual lithium clearance period.
5. Plasma renin activity, measured in 10 subjects, increased after the 600 mg dose of lithium carbonate (P < 0.005), but plasma concentrations of aldosterone and atrial natriuretic peptide were not significantly affected. Neither the 300 mg dose of lithium carbonate nor the placebo tablets affected hormone levels.
6. It is recommended that the test dose of lithium carbonate for use in lithium clearance studies should not exceed 300 mg.