Furosemide inhibits primarily the reabsorption of sodium and chloride not only in the proximal and distal tubules but also in the loop of Henle. The high degree of efficacy is largely due to this unique site of action. The action on the distal tubule is independent of any inhibitory effect on carbonic anhydrase and aldosterone.
The onset of diuresis following intravenous administration is within 5 minutes and somewhat later after intramuscular administration. The peak effect occurs within the first half hour. The duration of diuretic effect is approximately 2 hours.
Distribution
Furosemide is extensively bound to plasma proteins, mainly to albumin.
Plasma concentrations ranging from 1 to 400 mcg/mL are 91 to 99% bound in healthy individuals. The unbound fraction averages 2.3 to 4.1% at therapeutic concentrations.
Elimination
The terminal half-life of furosemide is approximately 2 hours.
Specific Populations
Furosemide binding to albumin may be reduced in elderly patients. Furosemide is predominantly excreted unchanged in the urine. The renal clearance of furosemide after intravenous administration in older healthy male subjects (60 to 70 years of age) is statistically significantly smaller than in younger healthy male subjects (20 to 35 years of age). The initial diuretic effect of furosemide in older subjects is decreased relative to younger subjects [see Use in Specific Populations (8.5)].
Based on PK results obtained from 51 premature infants (23-29 weeks gestational age (GA)) receiving repeated doses up to 4 times the maximum recommended total daily dose for intravenous (IV) administration (or 8 times the maximum recommended total daily dose for enteral administration), body weight and postnatal age were found to have an impact on furosemide clearance. Median clearance (normalized by dosing weight) was observed to increase from 8.9 (range: 2.1-21.2) ml/h/kg in infants with postnatal age (PNA) <30 days to 25.3 (range: 8.3 to 44.2) ml/h/kg in infants with PNA ≥30 days. In addition, higher clearance was observed in infants with higher body weight. Bioavailability of enteral dose compared to IV dose was estimated to be around 79%.
One study in six subjects demonstrated that the combination of furosemide and acetylsalicylic acid temporarily reduced creatinine clearance in patients with chronic renal insufficiency. There are case reports of patients who developed increased BUN, serum creatinine and serum potassium levels, and weight gain when furosemide was used in conjunction with NSAIDs.
Furosemide inhibits primarily the reabsorption of sodium and chloride not only in the proximal and distal tubules but also in the loop of Henle. The high degree of efficacy is largely due to this unique site of action. The action on the distal tubule is independent of any inhibitory effect on carbonic anhydrase and aldosterone.
The onset of diuresis following intravenous administration is within 5 minutes and somewhat later after intramuscular administration. The peak effect occurs within the first half hour. The duration of diuretic effect is approximately 2 hours.
Distribution
Furosemide is extensively bound to plasma proteins, mainly to albumin.
Plasma concentrations ranging from 1 to 400 mcg/mL are 91 to 99% bound in healthy individuals. The unbound fraction averages 2.3 to 4.1% at therapeutic concentrations.
Elimination
The terminal half-life of furosemide is approximately 2 hours.
Specific Populations
Furosemide binding to albumin may be reduced in elderly patients. Furosemide is predominantly excreted unchanged in the urine. The renal clearance of furosemide after intravenous administration in older healthy male subjects (60 to 70 years of age) is statistically significantly smaller than in younger healthy male subjects (20 to 35 years of age). The initial diuretic effect of furosemide in older subjects is decreased relative to younger subjects [see Use in Specific Populations (8.5)].
Based on PK results obtained from 51 premature infants (23-29 weeks gestational age (GA)) receiving repeated doses up to 4 times the maximum recommended total daily dose for intravenous (IV) administration (or 8 times the maximum recommended total daily dose for enteral administration), body weight and postnatal age were found to have an impact on furosemide clearance. Median clearance (normalized by dosing weight) was observed to increase from 8.9 (range: 2.1-21.2) ml/h/kg in infants with postnatal age (PNA) <30 days to 25.3 (range: 8.3 to 44.2) ml/h/kg in infants with PNA ≥30 days. In addition, higher clearance was observed in infants with higher body weight. Bioavailability of enteral dose compared to IV dose was estimated to be around 79%.
One study in six subjects demonstrated that the combination of furosemide and acetylsalicylic acid temporarily reduced creatinine clearance in patients with chronic renal insufficiency. There are case reports of patients who developed increased BUN, serum creatinine and serum potassium levels, and weight gain when furosemide was used in conjunction with NSAIDs.
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