Distribution, elimination and effect of furosemide in normal subjects and in patients with heart failure.

After furosemide 40 mg i. v. its plasma concentration was significantly higher during an 8-hour period in 6 patients with left sided heart failure than in 8 normal subjects. The plasma clearance was significantly lower in the patients than in the normal subjects--1.23 and 2.34 ml/kg/min, respectively. The apparently smaller volume of distribution in the cardiac patients (0.140 1/kg and 0.181 1/kg, respectively) was not significantly different. In the group of normal subjects, whose ages ranged from 27 to 74 years, no correlation was found between age and either plasma clearance or volume of distribution. In all the patients, the renal clearance of furosemide rose from the first to the second hour after the injection (average +/- SD)--39 +/- 17 and 77 +/- 51 ml/min. In normal subjects, the average values did not change--116 +/- 79 and 117 +/- 54 ml/min. The urinary excretion of furosemide and a metabolite (probably a glucuronide) was measured in 16 individuals. 24-hour urines from all the subjects investigated contained between 20 and 30 mg unchanged furosemide (average 25.2 mg). In addition, between 2.7 and 11.2 mg (average 6.7 mg) furosemide was excreted as the metabolite in five patients who had been treated with furosemide for at least the preceding 6 months. An average of 0.8 +/- 0.8 mg of the metabolite was found in 11 subjects who had not previously been treated with furosemide.