Determinants of furosemide delivery to its site of action.

We have investigated the pharmacokinetic determinants of delivery of furosemide to its site of action in the renal tubules in patients and healthy volunteers. The bioavailability of furosemide is low and variable. Patients with renal disease may also have a low renal extraction of furosemide. In clinically relevant concentrations the free fraction of furosemide is inversely proportional to the plasma albumin concentration. A change in the free fraction of furosemide will change Clr, Clnr, and Vd in the same direction and that will cause minimal changes in the excretion rate of furosemide and its t1/2. A change in RBF will change the secretory clearance of furosemide to the same proportion and consequently also the excretion rate and its t1/2.