The Effects of Diuresis on the Pharmacokinetics of the Loop Diuretics Furosemide and Torsemide in Patients with Heart Failure

Purpose: To evaluate the pharmacokinetics of furosemide and torsemide before and after diuresis in patients presenting with marked fluid overload. Subjects and Methods: We studied 44 patients with New York Heart Association class III or IV heart failure, ejection fraction ≤40%, and an estimated excess fluid body weight ≥6.8 kg. Oral furosemide or torsemide was administered before and after diuresis. Pharmacokinetic parameters were assessed before and after diuresis. Results: Following diuresis, maximum plasma concentration increased from 11.0 ± 5.0 μg/mL to 13.9 ± 6.8 with torsemide (P<0.05) and from 3.1 ± 1.5 to 3.9 ± 1.9 with furosemide (P = 0.16). Maximum concentration increased by more than 30% in only one third of the patients. Total absorption (by area under the curve method) increased 6% among patients on torsemide (P = 0.38) and 7% among patients on furosemide (P = 0.63) and increased >30% in only 1 torsemide and 2 furosemide patients. The time to maximum concentration decreased from 1.40 ± .82 h to 0.81 ± 0.36 with torsemide (P<0.01). There were no differences between furosemide and torsemide in the effects of edema on absorption. Conclusion: Marked diuresis altered the pharmacokinetics of both furosemide and torsemide in only a small percentage of patients. The use of adequate doses of oral diuretics in edematous patients may be successful, thereby permitting home treatment with oral diuretics and avoiding the cost of hospitalizations or home intravenous administration services.