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 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.
Mast Therapeutics, 12390 El Camino Real, Suite 150, San Diego, CA, 92130, USA, memanuele@mastthera.com.
Martin
M
Emanuele
Balu
B
Balasubramaniam
D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D020442:Poloxamer / Q000008:administration & dosage / Q000009:adverse effects* / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D055815:Young Adult
D020442:Poloxamer