Impact of Albumin Binding Function on Pharmacokinetics and Pharmacodynamics of Furosemide

Abstract

Background and Objectives: Albumin binding of the loop diuretic furosemide forms the basis for its transport to the kidney and subsequent tubular secretion, which is a prerequisite for its therapeutic effects. Accordingly, high albumin concentrations should result in higher efficacy of furosemide. However, study results on the combination of furosemide in conjunction with albumin, and on the efficacy of furosemide in hypoalbuminemia, did not confirm this hypothesis. The aim of this study was to determine the efficacy of furosemide not only in relation to albumin concentration, but also taking albumin function into account. Materials and Methods: In a prospective and non-interventional clinical observational trial, blood and urine samples from 50 intensive care patients receiving continuous intravenous furosemide therapy were evaluated. Albumin binding capacity (ABiC) determination allowed conclusions to be drawn about the binding site-specific loading state of albumin, by quantifying the unbound fraction of the fluorescent marker dansylsarcosine. In addition, assessment of the total concentration of furosemide in plasma and urine, as well as the concentration of free furosemide fraction in plasma, was performed by HPLC–MS. The efficacy of furosemide was evaluated by the ratio of urine excretion to fluid intake. Results: In patients with an ABiC ≥ 60% free furosemide fraction was significantly lower compared to patients with a lower ABiC (p < 0.001), urinary furosemide concentration was higher (p = 0.136), and a significantly higher proportion of infused furosemide was excreted renally (p = 0.010). ABiC was positively correlated (r = 0.908, p = 0.017) with increase in the urine excretion to fluid input ratio after initiation of furosemide therapy. Conclusions: ABiC could serve as a marker for individual response to furosemide and could be used to generate patient-specific therapeutic regimens. In view of the relatively low number of patients in this study, the relationship between furosemide efficacy and albumin function should be investigated in larger studies in the future.

Exploring Albumin Functionality Assays: A Pilot Study on Sepsis Evaluation in Intensive Care Medicine

“…These factors give rise to physiological alterations that do not only impact the concentration of serum albumin but also affect its binding and detoxification capabilities. In patients suffering from critical illnesses, the related dysfunction of albumin may aggravate the pathophysiological conditions and hamper the prognosis for patients of these conditions [ 14 , 25 , 31 , 37 ].…”

“…The disparities in the applied ligands may lead to variations in diagnostic performance depending on specific patient populations. ABiC employs dansyl sarcosine, which characterizes the binding capacity of albumin’s Sudlow side II, an area likely to be affected by disease-specific ligands, such as drugs or toxins [ 16 , 17 , 36 , 37 ]. On the other hand, EPR utilizes fatty acids known to interact with seven binding sites of albumin distributed across the protein, thereby encompassing Sudlow sides I and II as well [ 43 ].…”

Binding and detoxification efficiency of albumin decline after haemodialysis

“…Third, knowledge about using albumin binding competitors to promote the removal of protein-bound uraemic toxins and the benefit of understanding albumin functional properties for clinical decisions, e.g. patient-specific therapeutic regimens, have to be further investigated and need to be mutually integrated [ 25 , 26 ].…”

Management of cirrhotic ascites: Seven‐step treatment protocol based on the Japanese evidence‐based clinical practice guidelines for liver cirrhosis 2020

“…As diuretics have no therapeutic effect on hypoalbuminemia, and, importantly, conventional diuretics cannot exert their effects until they bind to albumin, it is crucial to improve hypoalbuminemia when administering diuretics 11,12 . The efficacy of loop diuretics such as furosemide may be reduced in the presence of hypoalbuminemia because furosemide is highly bound to albumin, and this binding is necessary for its transport into the kidney where it is separated from albumin in the proximal renal tubule and then secreted to its site of action 22,23 …”

“…11,12 The efficacy of loop diuretics such as furosemide may be reduced in the presence of hypoalbuminemia because furosemide is highly bound to albumin, and this binding is necessary for its transport into the kidney where it is separated from albumin in the proximal renal tubule and then secreted to its site of action. 22,23 Therapeutic strategies to improve hypoalbuminemia include the administration of branched-chain amino acids (BCAAs) and administration of human albumin. In animal studies, BCAA promoted albumin synthesis.…”