Nasal spray form of bumetanide may be just as good as oral, IV
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Key takeaways:
- A nasal spray version of the diuretic bumetanide showed equivalence to oral and IV versions.
- A nasal formulation could help patients with heart failure overcome diuretic resistance.
CHICAGO — A novel nasal spray formulation of bumetanide, a commonly used diuretic for patients with HF, had similar safety, tolerability, relative bioavailability and pharmacodynamics to the oral and IV versions, researchers reported.
The results of the phase 1 RSQ-777-02 study of nasal, oral and IV bumetanide in healthy volunteers were presented at the American Heart Association Scientific Sessions and simultaneously published in Circulation.
“We wanted to see if this therapy can help us overcome the challenge that we see in diuretic resistance in our heart failure patients,” Daniel Bensimhon, MD, medical director of the advanced HF and mechanical circulatory support program at Cone Health in Greensboro, North Carolina, said during a presentation. “Congestion ... is the most common cause of symptoms for our patients. We know that persistent congestion that is refractory leads to worse outcomes for our patients. About 90% of our patients who get admitted to the hospital have significant congestion. About 40% of these patients still have significant residual congestion when they leave the hospital. It is this inability to decongest patients that may lead to worse outcomes.
“By the time patients become symptomatic, there are an awful lot of physiological changes that make these patients diuretic-resistant,” including the development of gut edema, he said. “Just when our patients need therapy most, their oral diuretics often can fail them. [One study] found about two-thirds of the heart failure hospitalizations [in the U.S.] were done simply for the requirement of IV diuretics. They just had to overcome oral diuretic resistance. It costs about $17,000 per admission. That’s not good for the patients and not good for our health system. Is there a better way to do this, to get around diuretic resistance without using intravenous therapies? The intranasal delivery system is one with much interest. There’s a precedent for this; we use it for narcotic overdose with Narcan (naloxone), we use it for rescue therapy for people with migraine headaches and we also use it for disease states such as [vitamin] B12 deficiencies. It can be used as a way to get rapid therapy that overcomes the gut resistance to our diuretics.”
The study included 68 participants, of whom 66 completed it (mean age, 39 years; 34% women; 60% white). All were administered IV bumetanide once and oral and nasal bumetanide twice each, with a 48-hour washout period between administrations.
The primary endpoints of bioequivalence of nasal bumetanide to oral bumetanide as assessed by Cmax, an indicator of absorption rate, and by area under the curve were met, Bensimhon said during the presentation.
However, he said, Tmax, or time to Cmax, an indicator of the speed of the absorption rate, was 33% faster for nasal bumetanide than for oral bumetanide (1 hour vs. 1.5 hours).
Urine excretion at 2 hours and at 24 hours was similar across all three formulations, as was sodium excretion at those time points, he said.
The percentage of participants with at least one treatment-emergent adverse event was 16.2% for the nasal group, 23.9% for the oral group and 9.1% for the IV group, he said, noting one volunteer had nasal dryness after taking the nasal spray, but there were no cases of nosebleeds after nasal spray administration.
“Among a diverse group of healthy adults, nasal bumetanide was well tolerated and safe and had equivalent diuretic efficacy compared to IV and oral administration,” Bensimhon said during the presentation. “Intranasal bumetanide represents a novel, safe, self-adminstered parenteral diuretic option for our patients. I think the next question for us is to see if we can get to studies evaluating intranasal bumetanide in congested patients, which are forthcoming. Will this route really help us overcome diuretic resistance? If so, it could help us change our paradigm in patients who need decongestion and are not responding to their oral diuretic.”
In a discussant presentation, Ravi B. Patel, MD, MSc, assistant professor of medicine at Northwestern University Feinberg School of Medicine, said “today’s results offer a critical first step in understanding the role of nasal bumetanide spray in patients with worsening heart failure to prevent heart failure hospitalizations and improve symptoms.”
Reference:
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Bensimhon DR, et al. LBS.06. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2024; Chicago.
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