番茄社区

CHICAGO -- A bumetanide nasal spray in development for heart failure was well-tolerated and showed reliable rates of absorption compared with oral and intravenous delivery in a phase I trial of healthy volunteers.

The 68-person crossover study demonstrated bioequivalence of the intranasal loop diuretic in maximum concentration and under the concentration-time curve, reported Eric Adler, MD, of the University of California San Diego.

Both the nasal and IV forms of bumetanide had a variability in absorption of 27%, suggesting a more stable route of dosing compared with the oral formulation (>40%), according to findings presented at the American Heart Association (AHA) annual meeting.

Finally, the investigational product led to similar amounts of urine output and was associated with few adverse events (AEs), said Adler, including no significant nasal irritation.

Patients with acute decompensated heart failure are commonly prescribed the diuretic for fluid overload, he said, but gut absorption of oral bumetanide decreases over time and patients eventually require hospitalization to receive the IV version.

The new intranasal loop diuretic is "designed for absorption through the nasal mucosa, potentially providing more consistent bioavailability," Adler and colleagues explained in , where the study results were published simultaneously.

Dipti Itchhaporia, MD, of Hoag Heart and Vascular Institute in Newport Beach, California, and past president of the American College of Cardiology, stressed to 番茄社区 that more data are needed to see if the bumetanide nasal spray "has the same effect to reduce edema in heart failure patients."

Itchhaporia, who was not involved in the research, also pointed out that study participants "had assistance from a nurse in using the nasal spray. I question whether older, frail patients with heart failure would have the same success in using the device correctly."

"We need to have a study that answers that question," she said. "And then there is the question of costs, as all these new products tend to be expensive."

Adler and his fellow researchers indicated that they do plan to conduct further trials in patients with heart failure.

Their phase I RSQ-777-02 study was conducted from December 2023 through April 2024 in people without heart failure and who were not at risk for the condition. Participants had an average age of 39 years and two-thirds were men, while about 60% were white, 28% Black, 10% Asian, and 12% Hispanic. Mean body mass index was 26.2.

Participants were monitored at a research facility for 10 days while the three forms of bumetanide were given to each in a varied order, with a 48-hour washout period between treatments. As noted, the bumetanide nasal spray was delivered by a nurse.

Pharmacodynamic (PD) markers included total urine volume, natriuresis, and potassium excretion, and the researchers stated that the PD effects of the nasal spray on diuresis and natriuresis "were comparable to both IV and oral bumetanide."

Nasal bumetanide was absorbed 33% faster than the oral version, but slower than the IV version. However, the onset of sodium excretion through urine was faster with the nasal product.

Overall, about 38% of participants experienced at least one treatment-emergent AE, most commonly hypovolemia and headache. Treatment-emergent AEs occurred in 8.8% of participants after the bumetanide nasal spray, as compared with 9.1% and 17.9% with the IV and oral formulations, respectively. None of the treatment-emergent AEs were severe or life-threatening.

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