The pharmacokinetics and pharmacodynamics of furosemide in the anaesthetized dog

The correlation between pharmacokinetics and dynamics of furosemide was investigated in anaesthetized dogs. After intravenous administration (i.v.) of furosemide (5 mg/kg), the plasma concentration declined rapidly with bioexponential decay. The half-life (t1/2 beta) of the late phase of elimination was 0.931 +/- 0.187 h and the apparent volume of distribution at steady state was 0.25 +/- 0.043 l/Kg. The total clearance (Cltot) was 0.435 +/- 0.031 l/h/kg, in which the renal clearance was 0.260 +/- 0.020 (about 60% of Cltot). The change in rate of urinary excretion of furosemide was similar to the plasma concentration decay curve. The diuretic effect of furosemide was accompanied by an extreme increase in the excretion rate of sodium and chloride, but not potassium. The relationships between the diuretic response and the plasma concentration or the urinary excretion rate of furosemide was depicted by sigmoidal dose-response curves in both cases. The half-maximum effect was obtained at 1.5 micrograms/ml of plasma concentration or at 80 micrograms/min of excretion rate of furosemide.