Pharmacokinetics and pharmacodynamics of high dose furosemide in patients with chronic renal failure or nephrotic syndrome

Abstract

The pharmacokinetics and pharmacodynamics of repeated oral administration of furosemide were studied in patients with chronic renal failure or nephrotic syndrome using three different dosage regimens (4 x 40, 4 x 80 and 4 x 250 mg/d). Concentrations of the unchanged drug in serum and urine were measured fluorometrically. The elimination kinetics of furosemide was linear over the dose range studied. In contrast, the bioavailability of this diuretic decreased with increasing doses. The diuretic effects of all three dosage regimens were distinct only on the first day of therapy, thereafter decreasing rapidly. It can be concluded that the hormonal regulation of water and electrolyte balance are responsible for this behavior rather than pharmacokinetics. Creatinine and urea nitrogen excretion were not influenced by any furosemide dosage regimen.