Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function

Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function

Poloxamer 188 (P188) is a non-ionic amphiphilic copolymer with hemorheologic, antithrombotic, anti-inflammatory, and cytoprotective properties. It potentially has clinical utility in diverse diseases, such as acute myocardial infarction, acute limb ischemia, shock, acute stroke, heart failure, and s...

Full description

Bibliographic Details
Main Authors: Emanuele, Martin, Balasubramaniam, Balu
Format: Online
Language:English
Published: Springer International Publishing 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070458/
id pubmed-4070458
recordtype oai_dc
spelling pubmed-40704582014-07-16 Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function Emanuele, Martin Balasubramaniam, Balu Original Research Article Poloxamer 188 (P188) is a non-ionic amphiphilic copolymer with hemorheologic, antithrombotic, anti-inflammatory, and cytoprotective properties. It potentially has clinical utility in diverse diseases, such as acute myocardial infarction, acute limb ischemia, shock, acute stroke, heart failure, and sickle cell crisis. P188 is available as an excipient-grade product, manufactured to National Formulary specifications, which we refer to as P188-NF. During synthesis of P188-NF, polymerization of its polyoxyethylene and polyoxypropylene components generates undesirable low molecular weight (LMW) substances, such as truncated polymers and glycols. In early clinical studies, P188-NF yielded unexpected renal dysfunction. Here, we explore the nature of the renal dysfunction associated with P188-NF and use a purified (more homogenous) form of P188-NF (P188-P) to show that removal of LMW substances is associated with substantially less renal dysfunction. In both a remnant-kidney animal model and in clinical studies, P188-P demonstrates a substantially improved renal safety profile. Springer International Publishing 2014-04-11 2014-06 /pmc/articles/PMC4070458/ /pubmed/24723148 http://dx.doi.org/10.1007/s40268-014-0041-0 Text en © The Author(s) 2014 Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Emanuele, Martin
Balasubramaniam, Balu
spellingShingle Emanuele, Martin
Balasubramaniam, Balu
Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function
author_facet Emanuele, Martin
Balasubramaniam, Balu
author_sort Emanuele, Martin
title Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function
title_short Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function
title_full Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function
title_fullStr Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function
title_full_unstemmed Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function
title_sort differential effects of commercial-grade and purified poloxamer 188 on renal function
description Poloxamer 188 (P188) is a non-ionic amphiphilic copolymer with hemorheologic, antithrombotic, anti-inflammatory, and cytoprotective properties. It potentially has clinical utility in diverse diseases, such as acute myocardial infarction, acute limb ischemia, shock, acute stroke, heart failure, and sickle cell crisis. P188 is available as an excipient-grade product, manufactured to National Formulary specifications, which we refer to as P188-NF. During synthesis of P188-NF, polymerization of its polyoxyethylene and polyoxypropylene components generates undesirable low molecular weight (LMW) substances, such as truncated polymers and glycols. In early clinical studies, P188-NF yielded unexpected renal dysfunction. Here, we explore the nature of the renal dysfunction associated with P188-NF and use a purified (more homogenous) form of P188-NF (P188-P) to show that removal of LMW substances is associated with substantially less renal dysfunction. In both a remnant-kidney animal model and in clinical studies, P188-P demonstrates a substantially improved renal safety profile.
publisher Springer International Publishing
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070458/
_version_ 1612105995932139520

Similar Items