Clinical Pharmacology of Furosemide in Children: A Supplement
Furosemide is one of the most effective and least toxic diuretics used in pediatric practice. Experimental and clinical data suggest that adrenocorticosteroids and/or endogenous ouabain-like substances may play an important role in its diuretic effect. Also, the drug appears to have anti-inflammatory properties. In children with different diseases who received orally or intravenously 1 to 2 mg/kg doses of furosemide, a statistically significant positive linear relationship was found between the drug urinary excretion rate and the urine flow rate, but log dose-response curves to the drug were found to vary depending on the disease and the route of the drug administration. No sigmoid-shaped log dose-response curve (ie, one approaching a zero response at very low furosemide urinary excretion rates and a maximum response at very high excretion rates) was attained, which may suggest that the capacity of the kidney tubules to respond diuretically to the aforementioned doses of furosemide was not exceeded in these patients. However, in infants with different diseases and reasonably normal renal function who required administration of this diuretic, a very steep log dose-response curve to a 1 mg/kg intravenous dose of furosemide was found, which may suggest that higher doses may not result in a significant increase in diuretic response. The lowest mean furosemide urinary excretion rate and its concentration in urine associated with a significant diuresis were found to be 0.58 ± 0.33 μg/kg/min and 24.2 ± 10.5 μg/m l, respectively. Also, a significant correlation was found between the amount (in milligrams) of furosemide excreted in the urine during the first 6 hours after administration and the urine volume collected during that time. Patients with cystic fibrosis appeared to have a markedly more pronounced diuretic response to the average oral dose of 0.835 ± 0.18 mg/kg than that reported in control children given 2 mg/kg. In children with acute renal failure caused by acute gastroenterocolitis or glomerulonephritis, a broad relationship was observed between a single intravenous dose and diuretic response after administration of furosemide (1.2 to 30.8 mg/kg). It was suggested that the total daily dose of the drug should not exceed 100 mg in these patients. Furosemide was found to be effective in management of bronchoconstriction accompanying chronic lung disease and narrowing of the upper respiratory airways; in hydrocephalus in infancy to avoid cerebrospinal fluid shunts; in some diagnostic procedures, such as an assessment of fetal and neonatal hydronephrosis; and in evaluation of different types of renal tubular acidosis. Among side effects accompanying clinical use of this drug were cholelithiasis in premature infants receiving total parenteral nutrition concomitantly with the diuretic; secondary hyperparathyroidism and bone disease in infants obtaining long-term furosemide treatment; and drug-induced fever.