Diurnal Variations in Serum Lithium and Renal Lithium Clearance in Rats given Lithium as a Single Small Dose or as Multiple High Doses

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Abstract
Clearance determinations were carried out in three groups of rats: (1) A high lithium group given food to which 70 mmol/kg of lithium were added for 4–6 weeks leading to a mean serum lithium concentration of 0.85 mmol/l, (2) a low lithium group given food to which 15 mmol/kg of lithium were added for two days before the clearance period leading to a mean serum lithium concentration of 0.22 mmol/l, and (3) a group given the same food without lithium. The sodium and potassium contents of the food were kept high in order to avoid lithium-induced development of negative sodium balance and excessive polyuria. The rats were housed in four rooms with 6-hour displaced 24-hour light-dark cycles. The results showed that high doses of lithium led to a significant increase of the lithium clearance and the urine flow. Small amounts of lithium influenced neither the clearance values nor the urine flow. All renal variables were increased by about 50–100% during the dark period. The serum lithium concentration was least influenced by the diurnal rhythm. It is concluded that serum lithium concentrations measured at any time of the day are fairly representative of the 24 hours. A lithium clearance measured during daytime is valid for this period only. Long-term lithium treatment leads to an increase of the renal lithium clearance but does not diminish the normal diurnal rhythm of the kidney function.