Novel Bumetanide Nasal Spray Offers Potential Alternative to Oral and IV Diuretics in Phase 1 Trial

The phase 1 clinical study, published in the journal Circulation, has evaluated a novel intranasal formulation of bumetanide, demonstrating its safety and pharmacokinetic profile comparable to established oral and intravenous formulations.

Bumetanide, a loop diuretic widely used for managing fluid retention in conditions such as heart failure and renal disorders, has long been administered orally or intravenously. The new nasal spray formulation offers an alternative route of administration, potentially enhancing convenience and compliance in clinical settings.

Decompensated heart failure is often attributed to reduced absorption of oral diuretics caused by gut edema, frequently necessitating inpatient admission for intravenous diuretic therapy. Considering this, Andrew P. Ambrosy, Kaiser Permanente Northern California (KPNC) Division of Research, Pleasanton, CA, and colleagues conducted an open-label, randomized, controlled, crossover trial to evaluate the bioavailability of a novel bumetanide nasal spray compared to oral and intravenous formulations of the drug.

For this purpose, the researchers enrolled 68 healthy volunteers who received treatment with oral, intranasal, and intravenous bumetanide in one of four randomly assigned sequences, with each administration separated by a 48-hour washout period. Serum and urine samples were collected to evaluate the pharmacokinetics and pharmacodynamics of the drug.

The investigation revealed the following findings:

• The bumetanide nasal spray demonstrated statistical bioequivalence to oral bumetanide, meeting the primary endpoint.
• The nasal spray showed faster absorption, with a median time to a maximum concentration of 1 hour compared to 1.5 hours for oral administration.
• Pharmacodynamic effects on diuresis and natriuresis were comparable across the nasal, oral, and intravenous formulations.
• Treatment-emergent adverse events were reported in approximately 9% of participants after nasal and intravenous treatments and 18% after oral treatment, with hypovolemia and headache being the most common side effects.

The authors concluded that while establishing the proof of concept and ensuring long-term safety will require extensive further research, this phase 1 study provides promising evidence of the safety and efficacy of bumetanide nasal spray in a healthy population.

They emphasized that diuretic therapy has been a cornerstone of heart failure management for decades, making developing improved therapeutic options for patients a pressing need. The researchers hoped these findings would pave the way for phase 2 trials and inspire further innovative scientific exploration within this critical drug class.

"The introduction of a bumetanide nasal spray represents an innovative step in drug delivery technology, combining ease of use with effective pharmacological action. If validated in subsequent trials, this formulation could expand treatment options for patients requiring diuretic therapy, enhancing outcomes and quality of life," they wrote.

Reference:

Ambrosy AP et al. A randomized study comparing a novel intranasal formulation of bumetanide to oral and intravenous formulations. Circulation 2024 Nov 18; [e-pub]. (https://doi.org/10.1161/CIRCULATIONAHA.124.072949)