Poloxamer 188

Identification

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Name
Poloxamer 188
Accession Number
DB11333
Type
Small Molecule
Groups
Approved, Investigational
Description

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.

Synonyms
  • Pluronic F68
  • Poloxamer-188
  • Vepoloxamer
External IDs
MST-188
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Kang Du QingGel2.7 g/100gVaginalShenzhen Senton Science & Technology Co. Ltd2011-05-20Not applicableUs
Shur Clens Skin Wound Cleanser 24 Count Single Dose AmpulesLiquid200 mg/1mLTopicalConvaTec Inc2017-10-26Not applicableUs
Shur-clens Soln 20%LiquidTopicalConvatec, Division Of Bristol Myers Squibb Canada Co.1987-12-312006-07-31Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Lutrol F / Pluracare / Pluronic
Categories
UNII
LQA7B6G8JG
CAS number
691397-13-4

Pharmacology

Indication

Indicated to reduce viscosity in the blood before transfusions.

Pharmacodynamics

Poloxamer 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.

Mechanism of action

P188 seals stable defects in cell membranes induced by skeletal muscle cell membranes rupture induced by ischemia-reperfusion injury, electroporation, irradiation, and heat damage 2. The full mechanism of action of P188 in inducing cytoprotective effects is not clear; however, based on in vitro experiments and the structural similarity to plasmalemma, P188 may be directly incorporated into the phospholipid bilayer to attenuate the extent of tissue injury 1,2. Its high surface activity facilitates P188 to be inserted into lipid monolayers 4. P188 is proposed to exert localized actions by only interacting with damaged and compromised bilayers where the local lipid packing density is reduced 4. In addition to the direct interaction with the membrane, P188 was shown to inhibit MMP-9 protein levels and activity, as well as the NF-κB signal pathway, in the model of acute cerebral ischemia, which is associated with increased BBB permeability leading to cerebral edema and increased penetration 2. MMP-9 is a key factor in extracellular matrix (ECM) degradation and BBB disruption.

Additional Data Available
Adverse Effects

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Contraindications

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Absorption

Following 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 distribution

The 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 binding

The 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.

Metabolism

A 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 elimination

Renal clearance accounted for 90% of total plasma clearance in healthy male subjects 8.

Half life

In 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.

Clearance

Following a 48-hour continuous intravenous infusion of purified P188 in healthy volunteers, the mean total body clearance was estimated to be 4.40 ± 0.77 L/h when using the plasma concentration data only 8. Estimated mean renal clearance from the amount of P-188 excreted in urine was 5.21 ± 1.28 L/h 8. The clearance of a single metabolite HW1 was slower than the parent compound 8.

Toxicity

In 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.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

References

General References
  1. Moloughney JG, Weisleder N: Poloxamer 188 (p188) as a membrane resealing reagent in biomedical applications. Recent Pat Biotechnol. 2012 Dec;6(3):200-11. [PubMed:23092436]
  2. Gu JH, Ge JB, Li M, Xu HD, Wu F, Qin ZH: Poloxamer 188 protects neurons against ischemia/reperfusion injury through preserving integrity of cell membranes and blood brain barrier. PLoS One. 2013 Apr 16;8(4):e61641. doi: 10.1371/journal.pone.0061641. Print 2013. [PubMed:23613890]
  3. Curry DJ, Wright DA, Lee RC, Kang UJ, Frim DM: Surfactant poloxamer 188-related decreases in inflammation and tissue damage after experimental brain injury in rats. J Neurosurg. 2004 Aug;101(1 Suppl):91-6. doi: 10.3171/ped.2004.101.2.0091. [PubMed:16206978]
  4. Maskarinec SA, Hannig J, Lee RC, Lee KY: Direct observation of poloxamer 188 insertion into lipid monolayers. Biophys J. 2002 Mar;82(3):1453-9. doi: 10.1016/S0006-3495(02)75499-4. [PubMed:11867460]
  5. Hunter RL, Luo AZ, Zhang R, Kozar RA, Moore FA: Poloxamer 188 inhibition of ischemia/reperfusion injury: evidence for a novel anti-adhesive mechanism. Ann Clin Lab Sci. 2010 Spring;40(2):115-25. [PubMed:20421622]
  6. Murphy AD, McCormack MC, Bichara DA, Nguyen JT, Randolph MA, Watkins MT, Lee RC, Austen WG Jr: Poloxamer 188 protects against ischemia-reperfusion injury in a murine hind-limb model. Plast Reconstr Surg. 2010 Jun;125(6):1651-60. doi: 10.1097/PRS.0b013e3181ccdbef. [PubMed:20517088]
  7. Curry DJ, Wright DA, Lee RC, Kang UJ, Frim DM: Poloxamer 188 volumetrically decreases neuronal loss in the rat in a time-dependent manner. Neurosurgery. 2004 Oct;55(4):943-8; discussion 948-9. [PubMed:15458603]
  8. Grindel JM, Jaworski T, Emanuele RM, Culbreth P: Pharmacokinetics of a novel surface-active agent, purified poloxamer 188, in rat, rabbit, dog and man. Biopharm Drug Dispos. 2002 Apr;23(3):87-103. doi: 10.1002/bdd.297. [PubMed:12173548]
External Links
PubChem Substance
347911189
ChEMBL
CHEMBL2108134
MSDS
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of Vepoloxamer / Renal Impaired1
1CompletedBasic ScienceHealthy Volunteers1
2CompletedHealth Services ResearchDrug Action Increased1
2TerminatedTreatmentAcute Limb Ischemia1
2TerminatedTreatmentChronic Heart Failure (CHF)1
3CompletedTreatmentNeuropathic Pain Secondary to Radiation Therapy1
3CompletedTreatmentSickle Cell Disorders2
3CompletedTreatmentSickle Cell Disorders / Vaso-Occlusive Crises1
Not AvailableCompletedPreventionColonization / Line Insertion Site1
Not AvailableCompletedPreventionHealthy Volunteers1
Not AvailableUnknown StatusPreventionCentral Line-associated Bloodstream Infection (CLABSI) / Line Insertion Site1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
GelVaginal2.7 g/100g
LiquidTopical200 mg/1mL
LiquidTopical
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySoluble in cold waterMSDS
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Drug created on December 03, 2015 09:52 / Updated on November 02, 2019 02:44