EFFECTS OF ACUTE ADMINISTRATION OF ACETAZOLAMIDE AND FRUSEMIDE ON LITHIUM CLEARANCE IN HUMANS

To investigate the mechanism(s) of acute frusemide-induced increases in FE(Li), the effects of frusemide and acetazolamide, the carbonic anhydrase inhibiting agent, were evaluated in 19 healthy subjects either before or after pretreatment with acetazolamide or frusemide (11 subjects and eight subjects respectively). Acetazolamide pretreatment did not modify frusemide-induced increases in FE(Li) (DELTA-FLi 12.8 +/- 4.1% compared to 14.6 +/- 7.3%, P = NS); similarly, frusemide pretreatment did not modify acetazolamide-induced increases in FE(Li) (DELTA-FLi: 11.3 +/- 5.9% compared to 9.8 +/- 3.8%, P = NS). Acetazolamide-induced changes of FE(Li) were correlated significantly with acetazolamide-induced increases of FE(HCO3) (r = 0.61, P < 0.05), FE(Na) (r = 0.46, P < 0.05) but not of FE(Cl) (r = 0.25, P = NS). On the other hand, frusemide-induced changes of FE(Li) were correlated significantly with frusemide-induced increases of FE(Na) (r = 0.62, P < 0.005), FE(Cl) (r = 0.52, P < 0.025) but not of FE(HCO3) (r = 0.3, P = NS). Thus, frusemide effects on tubular lithium reabsorption are not related to carbonic anhydrase inhibition; furthermore, it appears that frusemide and acetazolamide affect lithium reabsorption by different and independent mechanism(s), possibly acting at different nephron site(s).