Kidney Week

Abstract: TH-PO114

Pharmacokinetics (PK) of Subcutaneous (SC) Furosemide (Furoscix) in CKD: A New Option for Outpatient Diuresis

Session Information

• Pharmacology
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

• 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

• Mende, Christian W., University of California San Diego, La Jolla, California, United States

Christian W. Mende, MD, FASN

• Luepke, Katie H., scPharmaceuticals, Burlington, Massachusetts, United States

Katie H. Luepke, PharmD

• Kamineni, Phanisyam, scPharmaceuticals, Burlington, Massachusetts, United States

Phanisyam Kamineni, PharmD, MPH

• Goodwin, Matthew M., scPharmaceuticals, Burlington, Massachusetts, United States

Matthew M. Goodwin, PharmD, MBA

• Mohr, John, scPharmaceuticals, Burlington, Massachusetts, United States

John Mohr, PharmD

• Cornelius, Barbara, scPharmaceuticals, Burlington, Massachusetts, United States

Barbara Cornelius

Background

Furoscix is approved as a 5-hour SC infusion via an on-body delivery device for treatment of congestion due to fluid overload in chronic HF. In a PK/PD study of HF patients, bioavailability was 99.6% with similar diuresis and natriuresis as IV furosemide. Purpose of analysis was to evaluate furosemide PK/PD in patients with reduced eGFR.

Methods

Furoscix 80 mg was administered SC over 5 hours in biphasic regimen (30 mg in 1st hr, 12.5 mg/hr remaining 4 hrs). IV furosemide was given as two 40 mg bolus doses 2 hours apart. Plasma was collected for furosemide concentrations and urine output (UO) was quantified over 24-hour period. Renal function was estimated using the Modification of Diet in Renal Diseases (MDRD) equation; results were stratified by eGFR. Patients with eGFR <45 mL/min/1.73m² were excluded from study.

Results

15 patients were available for analysis. Despite exclusion criteria, 2 patients were enrolled with eGFR <45 mL/min/1.73 m². Median (min-max) eGFR was 60 (41-98) mL/min/1.73 m². 7/15 (47%) patients had eGFR 60-89 mL/min/1.73 m², 7/15 (47%) had eGFR 30-59 mL/min/1.73 m², 1/15 (6%) had eGFR> 90 mL/min/1.73 m². As eGFR declined, furosemide levels increased but mean C_max values from SC were lower than IV. Regardless of eGFR, neither C_max from SC nor IV was associated with ototoxicity (>100,000 ng/mL). Mean (SD) 8-hour UO in patients with eGFR > 60 and <60 mL/min/1.73 m² from SC was 2818 (1034) and 2486 (1057) mL, respectively. 8-hour UO was consistent between SC and IV regardless of eGFR.

Conclusion

As eGFR declined, furosemide exposure from SC increased but remained below threshold for ototoxicity. UO between SC and IV remained consistent regardless of eGFR. Furoscix is new option for patients with CKD and fluid overload; future research needed for patients with eGFR <45 mL/min/1.73m².

Funding

• Commercial Support – scPharmaceuticals