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.