Distribution, Metabolism, and Excretion of a Novel Surface‐Active Agent, Purified Poloxamer 188, in Rats, Dogs, and Humans

Purified poloxamer 188 (PP188) is a nonionic, block copolymer surfactant with hemorheologic, antithrombotic, and anti‐adhesive properties. PP188 is being studied in phase III clinical trials in sickle cell disease and has been found to be well tolerated and has demonstrated benefit in ameliorating the effects of acute painful vasoocclusive crisis. The disposition of PP188 was studied in rats, dogs, and humans to establish a basis for understanding the safety parameters in support of clinical trials. PP188 was primarily distributed in extracellular water with little or no uptake by red blood cells, and had its highest concentrations in highly perfused tissues such as the kidney, liver, spleen, lymph nodes, and gastrointestinal tract. PP188 had no apparent effect on P450 isozymes in vitro. Metabolism was limited (