A novel, small-volume subcutaneous furosemide formulation delivered by an abdominal patch infusor device in patients with heart failure: results of two phase I studies

Abstract

Aims: Subcutaneous (SC) furosemide has potential advantages over intravenous (IV) furosemide by enabling self-administration or administration by a lay caregiver, such as facilitating early-discharge, preventing hospitalizations and in palliative care. A high concentration, pH neutral furosemide formulation has been developed for SC administration via a small patch-infusor pump. We aimed to compare the bioavailability, pharmacokinetic (PK) and pharmacodynamic (PD) profile of a new SC furosemide formulation with conventional IV furosemide, and describe the first use of a bespoke mini-pump to administer this formulation. Methods and results: A novel pH-neutral formulation of SC furosemide containing 80 mg furosemide in ∼2.7 mL (infused over five hours) was investigated. The first study was a PK/PD study of SC furosemide compared to 80 mg IV furosemide administered as a bolus in ambulatory patients with heart failure (HF). The primary outcome was absolute-bioavailability of SC compared to IV furosemide. The second study investigated the same SC furosemide preparation delivered by a patch infusor in patients hospitalized with HF. Primary outcome measures were treatment emergent adverse events, infusion site pain, device performance, and PK measurements.The absolute bioavailability of SC furosemide in comparison to IV furosemide was 112%, resulting in equivalent diuresis and natriuresis. When SC furosemide was administered via the patch pump there were no treatment emergent adverse events and 95% of participants reported no/minor discomfort at the infusion site. Conclusion: The novel preparation of SC furosemide had similar bioavailability to IV furosemide. Administration via a patch pump was feasible and well tolerated.