Furosemide Excretion Pathway and Timing
Furosemide (Lasix) is predominantly excreted unchanged in the urine through active tubular secretion by the proximal tubules, with a terminal half-life of approximately 2 hours in healthy individuals. 1
Primary Excretion Mechanism
Furosemide is excreted primarily unchanged in the urine through active secretion by the proximal renal tubules, which transport the drug into the tubular lumen before it reaches its site of action at the ascending limb of the loop of Henle. 1, 2
The drug is extensively bound to plasma proteins (91-99% bound to albumin at therapeutic concentrations), with only 2.3-4.1% remaining unbound and pharmacologically active. 1
Significantly more furosemide is excreted in urine following IV injection compared to oral administration (tablet or oral solution), though the bioavailability of oral furosemide ranges from 60-64% of IV dosing. 1
Timing of Excretion
The terminal half-life of furosemide is approximately 2 hours in healthy individuals, meaning the drug is substantially eliminated within 6-10 hours after administration. 1
After oral administration, the onset of diuresis occurs within 1 hour, with peak effect at 1-2 hours, and duration of diuretic effect lasting 6-8 hours. 1
The urinary excretion rate of furosemide directly correlates with urine flow rate and diuretic response, with the amount excreted in the first 6 hours after administration significantly correlating with total urine volume produced during that period. 3
Factors Affecting Excretion
Renal function is the primary determinant of furosemide excretion and response. Measured creatinine clearance strongly correlates with the amount of urinary furosemide excreted and is the most reliable predictor of urinary output response. 4
In acute kidney injury, both altered pharmacokinetics (reduced excretion) and reduced pharmacodynamic response occur, particularly when creatinine clearance falls below 40 mL/min/1.73 m². 4
Elderly patients demonstrate reduced renal clearance of furosemide compared to younger subjects, with statistically smaller clearance rates and decreased initial diuretic effect. 1
In congestive heart failure, renal and plasma clearance of furosemide correlate with renal function, which in turn correlates with left ventricular ejection fraction, though overall disposition kinetics may not differ significantly from healthy individuals. 5
Clinical Implications
It is the urinary concentration of furosemide, not plasma concentration, that determines diuretic efficacy, as the drug must be actively secreted into the tubular lumen to reach its site of action. 2
The minimum effective urinary excretion rate in pediatric patients is approximately 0.58 µg/kg/min with a urinary concentration of 24.2 µg/mL to produce significant diuresis. 3
Furosemide glucuronide is the only or major biotransformation product in humans, though the parent drug is predominantly excreted unchanged. 1