Furosemide kinetics and dynamics in patients with cirrhosis

Factors that influence intersubject variability in response to furosemide have been investigated in normal subjects and patients with cirrhosis. Furosemide pharmacokinetics and pharmacodynamics were measured in eight normal subjects and 14 patients with cirrhosis, eight of whom were resistant to diuretic therapy. Furosemide renal clearance decreased in proportion to creatinine clearance, whereas nonrenal clearance and volume of distribution were unchanged. These pharmacokinetic changes were, however, minimal and resulted in an only marginal alteration in the plasma concentration-time curve. The maximal rate of urinary sodium excretion decreased with reductions in creatinine clearance (r = 0.77). However, the extent of reduction in urinary excretion of sodium was proportionally greater than the reduction in creatinine clearance, whereas the rate of urinary furosemide excretion required to achieve 50% of maximal response did not change. Furosemide's pharmacokinetics were not, therefore, appreciably altered by cirrhosis. However, cirrhosis was associated with a reduction in pharmacodynamic response to this diuretic.