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.

中文翻译：

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一种新型小容量皮下速尿制剂，通过腹部贴片输注器装置输送至心力衰竭患者：两项 I 期研究的结果。

AIMS 皮下注射 (SC) 呋塞米比静脉注射 (IV) 呋塞米具有潜在优势，可以自行给药或由非专业护理人员给药，例如促进早期出院、防止住院和姑息治疗。已开发出一种高浓度、pH 中性的呋塞米制剂，用于通过小型贴片输液泵进行皮下注射。我们的目的是比较新型 SC 呋塞米制剂与传统 IV 呋塞米的生物利用度、药代动力学 (PK) 和药效学 (PD) 概况，并描述首次使用定制微型泵来给药该制剂。方法和结果 研究了一种新型 pH 中性速尿 SC 制剂，其中含有约 2.7 mL 中的 80 mg 速尿（输注超过 5 小时）。第一项研究是在流动性心力衰竭 (HF) 患者中进行皮下注射呋塞米与推注 80 毫克静脉注射呋塞米的 PK/PD 研究。主要结果是 SC 与静脉注射呋塞米相比的绝对生物利用度。第二项研究调查了通过贴片输注器向心衰住院患者输送相同的皮下速尿制剂。主要结局指标是治疗中出现的不良事件、输注部位疼痛、装置性能和 PK 测量。与静脉注射呋塞米相比，皮下注射呋塞米的绝对生物利用度为 112%，产生相同的利尿和尿钠排泄作用。当通过贴片泵皮下注射呋塞米时，没有出现治疗紧急不良事件，95% 的参与者报告输注部位没有/轻微不适。结论速尿皮下注射新制剂与静脉注射速尿具有相似的生物利用度。通过贴片泵给药是可行的并且耐受性良好。