Lithium-induced nephrotoxicity in rats following subcutaneous multiple injections and infusion using mini-osmotic...

The nephrotoxicity of the anti-manic-depressive drug lithium (Li) is well recognized but the effects of fluctuation in plasma levels from different Li dosage regimens are not. Experiments were done to compare the nephrotoxicity of Li in rats treated either with subcutaneous multiple injections (SMI) or by infusion using mini-osmotic pumps (MOP) vs concurrent controls. A dose of 2 meq/kg/day of LiCl dissolved in saline was given for 8 consecutive days. During treatment, the animals were kept in individual metabolism cages and their plasma Li levels, water intake, urine volume, pH, and osmolality were monitored daily. In the SMI group, average daily plasma Li levels, 30 min post-injection and just prior to the next injection, were 2.6 and 0.34 meq/liter, respectively. The daily mean plasma Li level in the MOP group was 0.39 meq/liter. While both Li treatment groups showed evidence of toxicity not seen in the respective controls, overall differences in the nephrotoxic response between the Li regimens emerged on Days 6 to 8. Thus water consumption and urine volume were both raised with SMI and by Day 8 the urine osmolality was reduced (all p less than 0.05). The results indicate that after administering equivalent amounts of Li, SMI treatment produced a higher degree of nephrotoxicity than the MOP treatment.