Pharmacokinetics and metabolism of furosemide in man

Abstract

The furosemide pharmacokinetics in healthy volunteers and in patients with renal insufficiency and hepatic cirrhosis is presented. On the average, 70 % of the oral furosemide dose is absorbed. The drug is 97.6 % bound to plasma albumins. The unbound fraction of the drug rapidly increases with albumin concentration below 2 gm per 100 ml. The half-life of furosemide ranges from 0.33 to 1.17 hours in healthy subjects, and from 4.9 to 9.7 hours in patients with advanced renal failure. In uremic patients with liver cirrhosis the elimination half-life is prolonged to more than 10 hours. Non renal clearance of furosemide is not affected by uremia; in uremic patients without liver disease about 60 to 98 % of intravenously administered dose of furosemide is excreted with bile within 24 hours. Only about 10 % of the drug is eliminated from the body during hemodialysis. The diuretic effect of furosemide is closely related to creatinine clearance: no effect in anuric cases, moderate effect if creatinine clearance is lower than 10 ml/min, and marked effect if creatinine clearance is higher than 10 ml/min 4-chloro-5-sulfamoylanthranilic acid is the only furosemide metabolite known so far. This metabolite is 1/4 as potent diuretic as the parent substance.