Pharmacokinetics of furosemide in normal subjects and functionally anephric patients.

Abstract

Furosemide pharmacokinetics were studied on 3 separate occasions in 4 hydropenic normal subjects. Single intravenous doses of approximately 0.5, 1.0, and 1.5 mg/kg were administered. The apparent volume of drug distribution was not affected by the dose and averaged 11.4 % of body weight. Mean plasma half‐life was 29.5 minutes with a clearance of 162 ml per minute. Renal excretion was the main route of elimination in these sub;ects and averaged 92% of the administered dose with a mean renal clearance of 149 ml per minute. This exceeded the glomerular filtration rate and suggested tubular secretion even though furosemide was 95% bound to plas'ma proteins. There was marked diuresis in all subjects, with a peak flow rate between 20 and 60 minutes after injection. Extracellular volume depletion was prevented by Ringer's lactate infusions. There was no significant difference in the peak fractional excretion of sodium with different doses. There was free water clearance during peak diuresis in all subjects, suggesting that furosemide does not affect the diluting segment of the nephron. In 5 functionally anephric patients, the distribution volume averaged 17.8% body weight, plasma half‐life was 80.7 minutes, and plasma clearance was 105 ml per minute. The data suggest a greater rate of nonrenal elimination than in normal subjects.