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FUROSEMIDE PHARMACOKINETICS

Furosemide pharmacokinetic parameters
Oral bioavailability (F) 65%
Clearance (CL) 7 L/h
Volume of distribution (Vd) 9 L
Half-life (t1/2) 1 h

Description

Furosemide is a diuretic that is used in anti-hypertensive therapy and for the relief of edema.
 
After oral administration furosemide is rapidly but incompletely absorbed, resulting in an oral bioavailability of ~60 %. Peak plasma drug concentrations are reached 1-2h after oral administration. Because furosemide is bound extensively to plasma proteins, its delivery to the tubules by filtration is limited. However, it is secreted efficiently by the organic acid transport system in the proximal tubule and thereby gains access to its binding sites on the Na-K-2Cl symporters in the luminal plasma membrane of the thick ascending limb.


Approximately 65% of furosemide is excreted unchanged in the urine, and the remainder is conjugated to glucuronic acid in the kidney. Accordingly, in patients with renal, but not liver, disease, the elimination half-life of furosemide is prolonged. The elimination half-life is short.

Clinical implications

The optimal drug plasma concentration depends on the targeted diuretic effect. About 1h after oral administration of 40 mg Furosemide, plasma drug concentrations of 2-3 microg/ml have been determined, and maximal plasma concentrations after i.v. injection of 40 mg Furosemide were 6-12 μg/ml.

Adverse effects of loop diuretics unrelated to the diuretic efficacy are rare, and most adverse effects are due to abnormalities of fluid and electrolyte balance. However, loop diuretics can induce ototoxicity.