Re-examination of the dose-response relationship for the renal effect of acetozolamide

Abstract

To examine the effect of acetazolamide on tubular reabsorption of bicarbonate, plasma concentrations of bicarbonate, K and PCO2 [partial pressure of CO2] were kept constant in volume expanded dogs. I.v. infusion of acetazolamide reduced glomerular filtration rate (GFR) at all dose levels; after a dose of 30 mg/kg body wt GFR was reduced by about 30% and was not reduced further by increasing the infused dose of acetazolamide up to 500 mg/kg body wt. When control GFR was restored by raising systemic blood pressure, increments in filtered and excreted bicarbonate were not significantly different. At control GFR a linear relationship was obtained between bicarbonate reabsorption and log dose when acetazolamide was administered i.v. in doses of 0.3-500 mg/kg body wt (r [correlation coefficient] = 0.93). Evidently, a log dose-response relationship applies over a 25 times larger dose range than previously assumed.