Abstract: TH-PO0096
Phasic and Net Sodium and Potassium Excretion After Extended-Release Torsemide Compared with Immediate-Release Torsemide and Furosemide: A Controlled Study in Volunteers
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Clinical Research
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Wilcox, Christopher Stuart, Georgetown University, Washington, District of Columbia, United States
- Pitt, Bertram, University of Michigan, Ann Arbor, Michigan, United States
- Anwar, Md Rafi, Sarfez Pharma Inc., Vienna, Virginia, United States
- Shah, Salim, Sarfez Pharma Inc., Vienna, Virginia, United States
Background
Loop diuretics cause acute natriuresis, a neutral phase and later sodium retention resulting in fluctuations in fluid and electrolyte excretion. We investigated how 24 mg extended-release torsemide (ERT) modifies this response compared with 20 mg immediate-release torsemide (IRT) or 40 mg furosemide (F).
Methods
Participants were admitted to a CRU for two and half consecutive days on 3 periods separated by 2 weeks. They received a controlled diet. Changes in Na+ and K+ excretion after dosing with the 3 diuretics were compared with those during the corresponding time intervals on the pre-dose control day at 0-4 h (natriuretic phase), 4-8 h (neutral phase), and 8-24 h (retention phase). Plasma and urine samples were used to assess pharmacokinetic parameters of ERT and IRT. Na+ and K+
Results
Eighteen volunteers were randomized, and 13 completed all 3 periods. Compared to IRT, ERT showed lower peak plasma concentration, prolonged time to peak but maintained total systemic exposure, demonstrating bioequivalence. Relative to IRT, ERT produced significantly less early natriuresis (122±15 vs 176±12 mmol/4hr; p=0.002), followed by significantly greater natriuresis during the neutral phase (34± 9 vs 10± 5 mmol/4hr; p=0.02), with a similar retention phase resulting in numerically higher, but not statistically significantly different 24 h natriuresis with ERT (92± 17 vs 69± 16 mmol). Compared to F, ERT produced similar early natriuresis (122± 15 vs 127± 18 mmol/4hr; p=0.82) but significantly lower early kaliuresis (3.6± 2.0 vs 10.7± 1.4 mmol/4 hours; p=0.0004), resulting in numerically lower, but not statistically significantly different, 24 h kaliuresis (11.7± 2.1 vs 12.7± 1.9 mmol; p=0.79). Overall, the 24 h urinary Na+:K+ ratio on the diuretic day was 7.6±1.9 for ERT, 7.0±2.3 for IRT, and 6.6±0.8 for F (p=0.03 vs ERT).
Conclusion
In this first head-to-head study, compared to IRT, ERT attenuates the early peak natriuresis, but prolongs it over 8 h. Compared to F, ERT has similar early natriuresis but reduced kaliuresis, indicating an additional flow-independent kaliuretic effect of F. These changes with ERT dampened diurnal fluctuations in electrolyte excretion and resulted in the highest 24 h post diuretic urinary Na+:K+ ratio, suggesting potentially improved clinical efficacy.
Funding
- Commercial Support – Sarfez Pharmaceutica Inc.