[Mechanisms of drug interactions with renal elimination of lithium]

Using indomethacin (2.5 mg/kg/day, i.m.) in rats, we confirmed the well-known interaction of NSAID's and the urinary elimination of lithium. This is due to an increase in the tubular reabsorption of lithium, probably associated with an increase in the reabsorption of sodium in the ascending limb of the loop of Henle, following inhibition of the synthesis of prostaglandins. With ramipril (1 mg/kg/day, p.o.), we confirmed an interaction with lithium pharmacokinetics in rats, also associated with an increase in the tubular reabsorption of sodium. In contrast, the angiotensin receptor antagonist losartan (10 mg/kg/day, p.o.) had no effect in this paradigm. Since the effects of ramipril were partially inhibited by an i.v. infusion of an antagonist of the bradykinin B2 receptor icatibant (0.1 mg/kg/day), we suggest that bradykinin contributes to the interaction between angiotensin converting enzyme inhibitors and renal excretion of lithium.