Is intranasal bumetanide a viable diuretic option in congestive HF?

Intranasal bumetanide appeared to be safe and efficacious as a self-administered parenteral diuretic option in a group of healthy volunteers. If it proves to be a safe and effective therapy for patients hospitalised for heart failure (HF) congestion, it may drastically reduce the number of patients that require hospitalisation.

“Congestion is the most common reason for patients with HF to require hospital admission,” according to Dr Daniel Bensimhon (Cone Health, NC, USA), “and in some cases, it is caused by resistance to oral diuretics” [1]. Two-thirds of the patients who are hospitalised for HF just require intravenous diuretics, which costs approximately 17,000 American dollars per patient per admission [2]. “We also see that a substantial proportion of patients is still congested at discharge, which increases the risk of re-hospitalisation. The question is whether an alternative parenteral delivery system can overcome diuretic resistance in congested patients and avoid their hospitalisation.

The current study tested bumetanide nasal spray (0.5 mg/device) for its pharmacokinetic and pharmacodynamic properties among healthy individuals (n=68). It was a randomised, open-label, 5-period crossover trial comparing the nasal option to oral and intravenous administration. The primary endpoints were maximum blood concentration of oral versus nasal formulations and the area under the curve (AUC) of oral versus nasal administration.

“Nasal and oral bumetanide displayed equivalent maximum blood concentration,” according to Dr Bensimhon [1]. “It was about 1/5^th of the intravenous concentration, which was expected.” The AUC data for bioavailability showed comparable outcomes as well. “The AUC for intravenous administration was not too different from oral and nasal administration,” said Dr Bensimhon. “Furthermore, we observed that time to maximum concentration was reached in 1 hour with nasal administration and in 1.5 hours with oral administration,” added Dr Bensimhon. An analysis of cumulative urine excretion demonstrated that the 3 ways of administration resulted in comparable outcomes. The intranasal administration method appeared to have similar safety outcomes as oral or intravenous administration options.

“Intranasal bumetanide was safe and resulted in equivalent diuretic efficacy as intravenous or oral administration of this agent in healthy volunteers, supporting further investigation of intranasal bumetanide among congested patients with HF,” decided Dr Bensimhon.

1. 
   
   1. Bensimhon D, et al. Randomised study comparing PK/PD properties of a novel intranasal formulation of bumetanide to oral and IV formulation. LBS.06, AHA Scientific Sessions 2024, 16–18 November, Chicago, USA.
   2. Greene SJ, et al. JACC Heart Failure 2020;8(11):943-953.

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Posted on 3 February 2025