Abstract 4359809: Effect of Subcutaneous (SC) Injection of Furosemide Compared with Intravenous (IV) Injection on Vital Signs in Healthy Volunteers

Introduction: Furosemide (FUR) remains the cornerstone agent to decongest patients with heart failure. Given the challenges associated with intravenous (IV) administration, an 80mg/10mL buffered formulation has been developed (Furoscix) to be administered subcutaneously (SC) over a period of 5 hours. This has demonstrated similar bioavailability and clinical efficacy to FUR IV with minimal impact on blood pressure (BP) and heart rate (HR). SCP-111 (FUR SC) is a novel SC injection FUR formulation in development with a concentration of 80mg/mL, and demonstrated similar bioavailability, diuretic, and natriuretic effects to FUR IV. However, its potential effects on BP and HR remain unknown. Methods: Randomized, open-label, single-center, crossover study. Healthy volunteers were randomized 1:1 to either receive 80mg FUR IV given as two 40mg boluses separated by two 2 hours first or FUR SC 80 mg/mL as SC injection over 10 seconds. Systolic BP (SBP), diastolic BP (DBP), and HR were monitored at set time points for 12 hours and changes from baseline were calculated. Following a 3-day washout period, individuals received the opposite treatment, and the same evaluation was completed. Results: The mean±SD baseline SBP and DBP for the FUR SC and FUR IV groups were 123±13 / 78±8 vs. 124±17 / 78± 9mmHg. Baseline HR were 69±9 and 69±10bpm, respectively indicating no difference between the groups. Mean change in SBP over the 12-hour follow-up ranged from -1.8 to -10.3mmHg for FUR SC and 1.5 to -11.3mmHg for FUR IV. The mean change in DBP ranged from 1.8 to -4.0mmHg for FUR SC and 5.5 to -3.7mmHg for FUR IV. The mean change in heart rate over the follow-up period ranged from 2.2 to -5.3bpm for FUR SC and 7.5 to -2.3bpm for FUR IV (Figure 1) . Conclusion: There were no clinically meaningful changes in blood pressure and heart rate over the 12-hour monitoring period in response to either FUR SC or FUR IV. Furosemide 80mg/mL administered as a SC injection was safe with regards to its effects on BP and HR and may become a potential alternative to IV furosemide in the near future.