2.1 Pharmacokinetics and diuretic effect
Furosemide is a commonly used diuretic listed on the WHO’s List of Essential Medicines which comprises the safest and most effective drugs readily available worldwide. It is a weak organic acid with low lipophilicity (log P = 2.03). It is 98.6 ± 0.4% bound to plasma protein due to its sulfonamide and carboxylic acid moieties which, together with a relatively short half-life of 1.3 ± 0.8 h and a low volume distribution (VD) of 0.13 ± 0.06 L kg-1, results in low tissue distribution. Clearance of furosemide is conducted predominantly in the kidneys (85%) with about half of it being metabolized to glucuronic acid and half being secreted unchanged.
To achieve a diuretic effect, furosemide is administered orally or intravenously, typically at doses of 40-80 mg. Furosemide blocks sodium (Na+), potassium (K+) and chloride (Cl-) reabsorption in the proximal and distal tubules as well as in the ascending limb of Henle’s loop and thereby causes diuresis peaking 60-90 min after administration with enhanced excretion of sodium, potassium and chloride. This diuretic effect is achieved by inhibition of the Na+/K+/Cl-cotransporters in the nephron, reducing Na+-transport from the luminal side into the basolateral side for reabsorption.