Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of furosemide.

The pharmacokinetics and pharmacodynamics of furosemide were evaluated after intravenous administration of the same total dose of furosemide in different lengths of infusion time (10 s, 30 min, 2 h, and 8 h) to 6 dogs. The fluid loss in urine was immediately replaced volume for volume with intravenous infusion of Lactated Ringer's solution. The pharmacokinetic parameters such as per cent of the dose excreted in urine, total body and renal clearances, and terminal half-life were not significantly different with four different infusion times. The volume of distribution at steady state and mean residence time based on venous data, on the other hand, appeared to increase with increasing infusion time. The mean values for Vss were 0.334, 0.478, 0.499, and 0.708 1 kg-1 for 10 s, 30 min, 2 h, and 8 h of infusion, respectively, and the corresponding values for MRT were 17.5, 22.2, 24.8, and 38.1 min. The diuretic effects (urine output and urinary excretion of sodium) were generally found to increase with increasing infusion times; the total mean 24 h urine outputs were 1102, 1464, 2190, and 3470 ml for 10 s, 30 min, 2 h, and 8 h of infusion, respectively, and the corresponding values for sodium excretion were 170, 175, 272, and 440 mmol. Furosemide plasma concentrations and hourly urinary excretion rates of furosemide, sodium, and potassium during the apparent steady state (between 2 and 8 h) in the 8 h infusion study were fairly constant.