Pharmacodynamic determinants of furosemide diuretic effect in children

The pharmacodynamics of 1 or 2 mg/kg of furosemide administered as a single dose orally or intravenously were studied in 34 hospitalized children (ranging in age from 9 days to 16.5 years) with normal renal function. These patients were divided into 3 groups: infants (furosemide 1 mg/kg, intravenously); children with steroid-responsive nephrotic syndrome (furosemide 2 mg/kg, orally and intravenously); patients with urinary tract infections and mild hypertension (furosemide 2 mg/kg, orally). A statistically significant positive linear relationship was found in these groups between the furosemide urinary excretion rate and urine flow rate, but log dose-response curves to furosemide were found to vary between the groups of patients studied. This variability reflects differences in the relationship between the amounts of furosemide reaching active sites and the pharmacodynamic effect of the drug. No sigmoid-shaped log dose-response curve (i.e., one approaching a zero response at very low furosemide urinary excretion rates, and a maximum response at very high excretion rates) was attained in this study. This suggests that the capacity of the kidney tubules to respond diuretically to the administered doses of furosemide was not exceeded in the studied patients. However, in the infants, a very steep log dose-response curve to a 1 mg/kg intravenous dose of furosemide suggests that higher doses may not result in a significant increase in diuretic response in infants with reasonably normal renal function. The lowest mean furosemide urinary excretion rate associated with significant diuresis was 0.58 +/- 0.33 micrograms/kg/min. Also, a significant correlation was found between the amount (in milligrams), of furosemide excreted in the urine during the first 6 h after administration and the urine volume collected during that time (r = 0.71; p less than 0.001; number of measurements = 43).