Toxicity and renal elimination of lithium in rats of different ages.

In 5- and 15-day-old rats, acute toxicity is much higher than in adults. However, in young rats two sublethal doses of lithium (75% of the LD50) can be injected in a shorter time interval than in adults, resulting in the same mortality (50%). After pretreatment of rats with 1.15 meq Li+/100 g b.wt. daily for 2 days and a load of 0.3 meq Li+/100 g b.wt. intraperitoneally on the day on which diuresis experiments were performed, a distinct age-dependence in renal lithium elimination was observed, with age-dependent consequences for the elimination of sodium and potassium. In the postnatal period, the ability to excrete lithium matures earlier than the ability to eliminate sodium. Thus the age-dependence of lithium toxicity stems from the age-dependent pharmacokinetic parameters of lithium, such as distribution and renal elimination.