Pharmacodynamics of the diuretic effects of aminophylline and acetazolamide alone and combined with furosemide in normal subjects

Abstract

The current study was performed in normal subjects to assess the mechanism of the natriuretic effects of aminophylline, to confirm the effect of acetazolamide on the proximal tubule and to assess the pharmacodynamics of the combination of aminophylline and of acetazolamide with furosemide. None of these agents or their combination affected renal hemodynamics. Aminophylline inhibited solute reabsorption at the diluting segment manifested by a 15% decrease in free water clearance relative to solute delivery (P less than .001). In addition, it decreased solute reabsorption in the proximal nephron. Acetazolamide affected only the proximal tubule. The combination of either aminophylline or of acetazolamide with furosemide was little different from furosemide alone. Analysis of dose-response curves to furosemide revealed a minor additive, i.e., parallel upward shift, of the dose-response curves with both combinations.