학술논문
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
Heart failure/cardiomyopathy
Heart failure/cardiomyopathy
Document Type
Report
Author
Source
European Heart Journal: Cardiovascular Pharmacotherapy. January 2024, Vol. 10 Issue 1, p35, 10 p.
Subject
Language
English
ISSN
2055-6837
Abstract
Introduction The ability to deliver furosemide subcutaneously (SC) rather than intravenously (IV) may result in opportunities to achieve a diuresis in clinical scenarios where parenteral administration is desirable but IV [...]
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) profiles 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 5 h) was investigated. The first study was a PK/PD study of SC furosemide compared with 80 mg IV furosemide administered as a bolus in ambulatory patients with heart failure (HF). The primary outcome was absolute bioavailability of SC compared with 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. Graphical Abstract Keywords Heart failure * Furosemide * Subcutaneous * Pharmacokinetics * Pharmacodynamics * Intravenous
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) profiles 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 5 h) was investigated. The first study was a PK/PD study of SC furosemide compared with 80 mg IV furosemide administered as a bolus in ambulatory patients with heart failure (HF). The primary outcome was absolute bioavailability of SC compared with 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. Graphical Abstract Keywords Heart failure * Furosemide * Subcutaneous * Pharmacokinetics * Pharmacodynamics * Intravenous