No abstract

We studied 10 patients with congestive heart failure to assess the dynamics of their response to 40 mg of furosemide. Patients excreted less sodium than normal controls: 142 +/- 36 and 245 +/- 16 mEq/4 hr (p < 0.05). Patients delivered the same amount of furosemide into the urine--14.9 +/- 2.0 and 18.7 +/- 2.1 mg/4 hr (p < 0.20)--but the time course of delivery differed. Normal subjects had a sigmoid-shaped curve when furosemide excretion rate was related to response. All patients but one had shifts in this curve and for a number of patients the configuration differed substantially from a sigmoid curve.

Changes in response to furosemide and other diuretics in patients with congestive heart failure (CHF) could occur because of disease-induced changes in absorption of the drug or changes in disposition which affect its access to its site of action. A difference was not found in the bioavailability of forosemide in patients with CHF compared to normal volunteers, 31 +/- 12 vs. 38 +/- 20% (mean +/- sd), respectively. Both groups showed considerable interindividual variability, though serial analyses within individuals revealed consistency. Amounts of furosemide delivered into the urine after an intravenous dose correlated significantly to that after an oral dose implying that the interindividual variability is not caused primarily by variability in absorption in either group. Overall, disposition kinetics of furosemide did not differ between groups. Because of heterogeneity of renal and cardiac function among the patients, we were able to demonstrate correlations of plasma and renal clearance of furosemide with renal function; in turn, renal function correlated with left ventricular ejection fraction. Consequently, some patients had changes in furosemide disposition, but, for the most part, differences in response to furosemide were caused by abnormal responses to, rather than changed handling of the diuretic.