Poloxamer 188

Approved, Investigational Small Molecule

Poloxamer 188

Poloxamer 188 (P188) is a nonionic block linear copolymer that exhibits rheologic, anti-thrombotic, anti-inflammatory, and cytoprotective activities in various tissue injury models 5. Composed of two hydrophilic side-chains attached to a hydrophobic center core 2, its average molecular weight is 8400 Daltons. P188 has been approved by the FDA for more than 50 years as a therapeutic agent to reduce viscosity in the blood before transfusions 1. Due to its sufactant properties, P188 may also be found in over-the-counter (OTC) products such as toothpaste, laxatives and mouthwash, and used in various cosmetic, industrial and pharmaceutical applications. There is an evidence of P188 increasing the structural stability and resealing of the plasma membrane via direct incorporation into the phospholipid bilayer 1. The ability of P188 in attenuating membrane damage and cell injury has been demonstrated in a variety of in vivo and in vitro models 2. The use of P188 as a potential treatment in different pathological conditions, such as chronic microvascular diseases and skeletal muscle deficiencies, is under investigation 1. Poloxamer 188 (P188) is a nonionic block linear copolymer that exhibits rheologic, anti-thrombotic, anti-inflammatory, and cytoprotective activities in various tissue injury models 5. Composed of two hydrophilic side-chains attached to a hydrophobic center core 2, its average molecular weight is 8400 Daltons. P188 has been approved by the FDA for more than 50 years as a therapeutic agent to reduce viscosity in the blood before transfusions 1. Due to its sufactant properties, P188 may also be found in over-the-counter (OTC) products such as toothpaste, laxatives and mouthwash, and used in various cosmetic, industrial and pharmaceutical applications. There is an evidence of P188 increasing the structural stability and resealing of the plasma membrane via direct incorporation into the phospholipid bilayer 1. The ability of P188 in attenuating membrane damage and cell injury has been demonstrated in a variety of in vivo and in vitro models 2. The use of P188 as a potential treatment in different pathological conditions, such as chronic microvascular diseases and skeletal muscle deficiencies, is under investigation 1.

Summary of Product Characteristics

Field Name Value
NamePoloxamer 188
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionPoloxamer 188 (P188) is a nonionic block linear copolymer that exhibits rheologic, anti-thrombotic, anti-inflammatory, and cytoprotective activities in various tissue injury models 5. Composed of two hydrophilic side-chains attached to a hydrophobic center core 2, its average molecular weight is 8400 Daltons. P188 has been approved by the FDA for more than 50 years as a therapeutic agent to reduce viscosity in the blood before transfusions 1. Due to its sufactant properties, P188 may also be found in over-the-counter (OTC) products such as toothpaste, laxatives and mouthwash, and used in various cosmetic, industrial and pharmaceutical applications. There is an evidence of P188 increasing the structural stability and resealing of the plasma membrane via direct incorporation into the phospholipid bilayer 1. The ability of P188 in attenuating membrane damage and cell injury has been demonstrated in a variety of in vivo and in vitro models 2. The use of P188 as a potential treatment in different pathological conditions, such as chronic microvascular diseases and skeletal muscle deficiencies, is under investigation 1.
External IDsMST-188
IndicationIndicated to reduce viscosity in the blood before transfusions.
PharmacodynamicsPoloxamer 188 (P188) exerts a protective action against oxidative stress and inflammation in tissue injury in various experimental models. In the rat model of excitotoxic injury, immediate intrathecal administration of P188 reduced neuronal loss, indicated by smaller spherical excitotoxic lesions 7. In a murine hind-limb model, P188 mediated a protective action against ischemia-reperfusion injury as indicated by decreased myocyte injury, preserved tissue adenosine 5'-triphosphate levels, and improved survival rates, suggesting that P188 can seal defects in cell membranes and attenuate damage induced by reactive oxygen species 6. P188 was shown to elicit protective effects against excitotoxic injury, and trauma-induced necrotic and apoptotic cell death in cultured neurons 2. In the mouse stroke models, P188 exerted a neuroprotective effect in brain ischemia-reperfusion induced acute injury by significantly reducing infarct volume and water content in brain edema and ameliorating the neurological symptoms 24 h after ischemia or reperfusion injury 2. P188 also significantly inhibited inflammatory, coagulation, and apoptotic responses resulting from superior mesenteric artery occlusion 5. In the experimental model of striatum injury in rats, P188 was shown to reduce excitotoxicity-induced tissue loss and macrophage infiltrate 3.
AbsorptionFollowing a 48-hour continuous intravenous infusion of purified P188 in healthy volunteers, the mean concentration of P188 at steady state concentration (Css) was 522 ± 118 mg/L and the maximum concentration occurring at the end of the loading dose was approximately 909 ± 165 mg/L 8. The plasma concentrations were dose-proportional 8.
Volume of distributionThe volume of distribution at steady state (Vss) after a continuous intravenous infusion of 500 mg/kg of P188 on day 7 was approximately 2.13 mL/kg in pregnant female rats 8. Vss was 876 mL/kg in dogs receiving a dose of 720 mg/kg/day 8.
Protein bindingThe exact protein binding profile of P188 has not been determined due to the apparent formation of micelles that caused excessive non-specific binding to ultrafiltration and dialysis membranes 8. Based on the findings of a protein binding interaction studies, P188 displayed no clinically significant human plasma binding characteristics 8.
MetabolismA single metabolite, HW1, with a molecular weight of approximately 16000 Daltons was detected in a pharmacokinetic study in dogs and man. HW1 was present in 10-20 and 40% of the parent compound at steady state in dogs and humans, respectively 8. However, it is suggested that block polymers are not metabolized and are excreted unchanged in the urine and feces, and HW1 may be a component of the higher molecular weight distribution of P188 that concentrates in the plasma due to its lower clearance rate 8.
Route of eliminationRenal clearance accounted for 90% of total plasma clearance in healthy male subjects 8.
Half lifeIn humans, P188 has half-life of 18 hours 1. The terminal plasma elimination half-life was approximately 7.65 ± 1.10 hours in healthy volunteers receiving a 48-hour continuous intravenous infusion of purified P188 8.
ToxicityIn an acute oral toxicity study in rat, the LD50 was 9380 mg/kg MSDS. P188 has been demonstrated to be safe when given for up to 72 hours 1.