Polyethylene glycol 400

Identification

Summary

Polyethylene glycol 400 is an ingredient used in a wide variety of medications, and is not an approved medication.

Brand Names
Blink Tears, Colirio Ocusan, Leader Lubricant Eye Drops, QC ultra lubricant eye, Systane, Tears Lubricant, Visine Advanced Relief, Visine Dry Eye Relief, Visine Maximum Redness Relief, Visine Tired Eye Relief, Visine Totality
Generic Name
Polyethylene glycol 400
DrugBank Accession Number
DB11077
Background

Polyethylene glycols (PEGs) are products made of condensed ethylene oxide and water that can contain various derivatives and have various functions. Because many PEG types are hydrophilic, they are favorably used as enhancers of penetration, and used heavily in topical dermatological preparations. PEGs, along with their many nonionic derivatives, are widely utilized in cosmetic products as surfactants, emulsifiers, cleansing agents, humectants, and skin conditioners.9

Polyethylene glycol 400 (PEG 400) is a low-molecular-weight grade of polyethylene glycol with a low-level toxicity. It is very hydrophilic, which renders it a useful ingredient in drug formulations to augment the solubility and bioavailability of weakly water-soluble drugs. It is used in ophthalmic solutions for the relief of burning, irritation and/or discomfort that follows dryness of the eye 7. PEG "400" indicates that the average molecular weight of the specific PEG is 400 10.

PEGylation occurs when PEGs are attached to numerous protein medications, allowing for greater solubility for selected drugs. Examples of PEGylated medications are PEG-interferon alpha (Pegintron) and PEG-filgrastim. In addition, PEG is available as a bowel preparation for colonoscopy procedures and as a laxative 10.

Type
Small Molecule
Groups
Approved
Synonyms
  • 3,6,9,12,15,18,21-heptaoxatricosane-1,23-diol
  • Octaethylene glycol
  • PEG-400
  • PEG-8
  • Polyethylene glycol 400
  • Polyethylene glycol 8

Pharmacology

Indication

PEG-400 has been indicated for the temporary relief of burning and irritation due to dryness of the eye, and for protection against further irritation and desiccation 14, 15, 16.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

PEG, when used as PEG-400 for eye lubrication provides relief of dry eye symptoms and prevents further irritation, thus protecting the eye from injury 15. PEG allows comfortable eye drop/natural tear instillation by offering improved spreading of the drop over the ocular surface with diminished blurring 14,15.

Mechanism of action

PEG, depending on molecular weight, has various mechanisms of action 4, 5, 6, 7. For the purpose of Peg-400, the mechanism of action on the eye tissues will be the primary focus of discussion.

PEG-400 is considered a lacrimomimetic, or a synthetic ocular lubricant that improves one or more components of the lacrimal film by augmenting the tear volume and stability and by protecting the eye surface against desiccation 16. Hydroxypropyl-guar (HPG) is used along with polyethylene glycol 400 (PEG) and propylene glycol (PG) as a gelling agent that conforms to abnormalities of the tear film and existing irregularities on the ocular surface 16.

PEG provides lubrication and acts as a surfactant by coating the eye and interacting with propylene glycol and other solutions that help to act as surfactants on the eye mucosa 15. This allows for long-lasting, soothing effects 15.

Recent studies involving nanoparticle drug delivery have demonstrated that PEG can achieve sustained drug delivery. The delivery of drugs to mucosal surfaces is a significant challenge due to the presence of the protective mucus layer that acts to trap and quickly remove foreign particles. Nanoparticles designed to rapidly cross mucosal barriers (mucus-penetrating particles, “MPP”) have proven promising for augmenting drug distribution, and efficacy at various mucosal surfaces. Mucus- penetrating particles are heavily coated with polyethylene glycol (PEG), protecting the nanoparticle core from adhesion with mucus 17.

Polyethylene glycol, when free in solution, may also demonstrate attraction to the surfaces of various types of vesicles, cells or macromolecules, leading to polymer adsorption and subsequently either a repulsion or to an attraction, via bridging, of the surfaces or vesicles—again strongly depending on the temperature, molecular weight, and concentration of the polyethylene glycol. Low molecular weight polyethylene glycol (such as PEG-400) generally promotes cells or vesicles to adhere (depletion attraction), high molecular weight polyethylene glycol causes them to repel 18.

TargetActionsOrganism
UEctonucleotide pyrophosphatase/phosphodiesterase family member 1
other
Humans
UOxidoreductase HTATIP2Not AvailableHumans
Absorption

PEG has low toxicity profile with an absorption of less than 0.5% 10.

Topical absorption of PEG occurs and, demonstrates a molecular weight dependence similar to that of PEG given orally. Absorption by this route is likely to be poor 12.

Volume of distribution

Not Available

Protein binding

Despite that fact that PEG is believed to be an excellent material to resist protein adsorption, there is a lack of quantitative evidence regarding interactions between proteins and PEG. A study has been performed that suggests that a large number of PEG molecules could associate with protein molecules 3.

Metabolism

The metabolism of PEG involves the oxidation of the alcohol groups located on the PEG to a carboxylic acid. For example, the diacid and hydroxyl acid metabolites of PEG have been measured in the plasma and urine of burn patients and rabbits and in the bile of cats. In the isolated guinea pig liver and in rat/guinea pig in vitro, PEG has demonstrated to be sulfated. Evidence from experiments with PEG400 suggests that ethylene glycol is not formed as a metabolite of PEG in humans. Negligible amounts of oxalic acid are liberated after the metabolism of PEG 12.

The first phase of metabolism of PEG in mammals is regulated by the enzyme alcohol dehydrogenase. Liver cytochorome P450 enzymes may also play a role in the oxidation of PEG, although the evidence for this is not clear 12. Also, PEG has been shown to be metabolized by sulfotransferase enzymes. Although there is evidence that PEG can be metabolized to various phase 1 and phase 2 metabolites, the toxicology data presented above indicate that these metabolites are of very little toxicological concern. However, metabolism of PEG to the acid metabolite(s) has been implicated in the acidosis and hypercalcemia observed in patients after overdose 12. It is clear that these metabolites can be formed in multiple toxicology species and that the phase 1 metabolites are seen in animals and humans. These data indicate that humans and animals will be exposed to similar metabolites after administration of PEG 12. metabolic clearance of PEG decreases markedly as molecular weight increases. For PEG400, up to 25% of the dose may be metabolized in humans (Schaffer et al., 1950); similar results are also seen in the rabbit 12.

The absorption of PEG by the oral route is molecular weight- dependent. Urinary recovery data for PEG400 indicate that 50 to 60% of PEG with this molecular weight is absorbed from the intestine 12. In the case of PEG-400, up to 25% of the dose may be metabolized in humans. Similar results have also been obtained in studies on the rabbit 12.

Route of elimination

Human excretion studies have demonstrated that 86% and 96% of PEG1000 and 6000 were excreted in the urine 12 h after intravenous administration. Specific data on PEG-400 are not available 12. In rats, urine PEG undergoes biliary excretion, and this process is depending on molecular weight, with hepatic clearance reaching a minimum at about 50 kDa molecular mass (in mouse)12.

Half-life

Great than 24h 11.

Clearance

In mice, lease than <10 % of the administered dose was cleared by the liver 12.

Adverse Effects
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Toxicity

PEG of different molecular weights by a range of routes has been studied extensively, and has not led to any major toxicities, and signs/symptoms of toxicity that do occur are only observed at a much higher than therapeutic dose 12.

LD50 = 157000 mg/kg, intragastric, guinea pigs MSDS LD50 = 28915 mg/kg, intragastric, mice, rats MSDS LD50 = 9708 mg/kg, intra-abdominal, rats MSDS LD50= 7312 mg/kg, intravenous, rats MSDS

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
No interactions found.

Products

Products
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International/Other Brands
CV single use lubricant eye drops / Good Neighbour Pharmacy Lubricant Eye Drops / Good Sense Lubricant Eye Drops
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Blink Gel TearsSolution / drops2.5 mg/1mLOphthalmicJohnson & Johnson Surgical Vision, Inc.2008-05-01Not applicableUS flag
Blink TearsSolution / drops2.5 mg/1mLOphthalmicJohnson & Johnson Surgical Vision, Inc.2016-03-15Not applicableUS flag
Blink TearsSolution / drops2.5 mg/1mLOphthalmicHolopack Verpackungstechnik GmbH2016-04-04Not applicableUS flag
Blink TearsSolution / drops2.5 mg/1mLOphthalmicJohnson & Johnson Surgical Vision, Inc.2008-03-172017-08-31US flag
Blink TearsSolution / drops2.5 mg/1mLOphthalmicJohnson & Johnson Surgical Vision, Inc.2008-02-01Not applicableUS flag
Dark Spot CorrectorCream.3 mg/15mgTopicalLange SAS2012-09-17Not applicableUS flag
Lightening Day CreamCream2.5 mg/50mgTopicalLange SAS2012-07-18Not applicableUS flag
Visine Dry Eye ReliefSolution / drops10 mg/1mLOphthalmicJohnson & Johnson Consumer Inc.2020-04-27Not applicableUS flag
Visine Dry Eye ReliefSolution / drops10 mg/1mLOphthalmicJohnson & Johnson Consumer Inc.2020-04-27Not applicableUS flag
Visine Dry Eye Relief Eye DropsSolution / drops10 mg/1mLOphthalmicJohnson & Johnson Consumer Inc.2020-04-27Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Advance Relief Eye DropsPolyethylene glycol 400 (1000 mg/100mL) + Dextran 70 (100 mg/100mL) + Povidone (1000 mg/100mL) + Tetrahydrozoline hydrochloride (50 mg/100mL)Solution / dropsOphthalmicWinCo Foods, LLC2015-01-09Not applicableUS flag
Advanced reliefPolyethylene glycol 400 (10 mg/1mL) + Dextran 70 (1 mg/1mL) + Povidone (10 mg/1mL) + Tetrahydrozoline hydrochloride (0.5 mg/1mL)LiquidOphthalmicAmerican Sales Company2011-09-07Not applicableUS flag
Advanced ReliefPolyethylene glycol 400 (10 mg/1mL) + Dextran 70 (1 mg/1mL) + Povidone (10 mg/1mL) + Tetrahydrozoline hydrochloride (0.5 mg/1mL)LiquidOphthalmicKareway Product, Inc.2018-05-30Not applicableUS flag
Advanced reliefPolyethylene glycol 400 (10 mg/1mL) + Dextran 70 (1 mg/1mL) + Povidone (10 mg/1mL) + Tetrahydrozoline hydrochloride (0.5 mg/1mL)LiquidOphthalmicSamchundang Pharm. Co., Ltd.2010-08-29Not applicableUS flag
Advanced Relief Eye DropsPolyethylene glycol 400 (1 % w/v) + Dextran 70 (0.1 % w/v) + Povidone (1 % w/v) + Tetrahydrozoline hydrochloride (0.05 % w/v)SolutionOphthalmicKc Pharmaceuticals, Inc.Not applicableNot applicableCanada flag
Advanced Relief Eye DropsPolyethylene glycol 400 (1 % w/v) + Dextran 70 (0.1 % w/v) + Povidone (1 % w/v) + Tetrahydrozoline hydrochloride (0.05 % w/v)SolutionOphthalmicTEVA Canada Limited2010-08-30Not applicableCanada flag
Artificial TearsPolyethylene glycol 400 (0.01 mg/1mg) + Glycerin (0.002 mg/1mg) + Hypromellose (0.002 mg/1mg)Solution / dropsOphthalmicNucare Pharmaceuticals,inc.2018-06-01Not applicableUS flag
Artificial TearsPolyethylene glycol 400 (10 mg/1mL) + Glycerin (2 mg/1mL) + Hypromellose (2 mg/1mL)LiquidOphthalmicAmerican Sales Company2010-09-06Not applicableUS flag
Artificial TearsPolyethylene glycol 400 (0.01 mg/1mg) + Glycerin (0.002 mg/1mg) + Hypromellose (0.002 mg/1mg)Solution / dropsOphthalmicPreferred Pharmaceuticals Inc.2021-03-11Not applicableUS flag
Artificial TearsPolyethylene glycol 400 (0.01 mg/1mg) + Glycerin (0.002 mg/1mg) + Hypromellose (0.002 mg/1mg)Solution / dropsOphthalmicGeri-Care Pharmaceuticals, Corp2018-06-01Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Dark Spot CorrectorPolyethylene glycol 400 (.3 mg/15mg)CreamTopicalLange SAS2012-09-17Not applicableUS flag
Lightening Day CreamPolyethylene glycol 400 (2.5 mg/50mg)CreamTopicalLange SAS2012-07-18Not applicableUS flag
PegPolyethylene glycol 400 (45 g/100g) + Polyethylene glycol (55 g/100g)CreamTopicalBiocellerex, Inc.2015-07-142016-01-05US flag

Categories

Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
B697894SGQ
CAS number
25322-68-3
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

References

General References
  1. Basit AW, Newton JM, Short MD, Waddington WA, Ell PJ, Lacey LF: The effect of polyethylene glycol 400 on gastrointestinal transit: implications for the formulation of poorly-water soluble drugs. Pharm Res. 2001 Aug;18(8):1146-50. [Article]
  2. Foulks GN: Clinical evaluation of the efficacy of PEG/PG lubricant eye drops with gelling agent (HP-Guar) for the relief of the signs and symptoms of dry eye disease: a review. Drugs Today (Barc). 2007 Dec;43(12):887-96. doi: 10.1358/dot.2007.43.12.1162080. [Article]
  3. Wu J, Wang Z, Lin W, Chen S: Investigation of the interaction between poly(ethylene glycol) and protein molecules using low field nuclear magnetic resonance. Acta Biomater. 2013 May;9(5):6414-20. doi: 10.1016/j.actbio.2013.01.006. Epub 2013 Jan 11. [Article]
  4. Polyethylene glyco [Link]
  5. SIGMA-ALDRICH PEG 400 [Link]
  6. Polyethylene glycol 400 (PEG400) affects the systemic exposure of oral drugs based on multiple mechanisms: taking berberine as an example [Link]
  7. Polyethylene glycol [Link]
  8. Polyethylene Glycol [Link]
  9. Safety Evaluation of Polyethylene Glycol (PEG) Compounds for Cosmetic Use [Link]
  10. PEG-400 [Link]
  11. Safety of Total Daily Doses of Polyethylene Glycol (PEG) 400 Administered Orally to Healthy Male Human Subjects [Link]
  12. PEGylated Proteins: Evaluation of Their Safety in the Absence of Definitive Metabolism Studies [Link]
  13. The Absorption and Excretion of a Liquid Polyethylene Glycol [Link]
  14. Polyethylene Glycol 400 [Link]
  15. Systane Mechanism of Action [Link]
  16. Ocular lubricants: what is the best choice? [Link]
  17. Impact of Surface Polyethylene Glycol (PEG) Density on Biodegradable Nanoparticle Transport in Mucus ex vivo and Distribution in vivo [Link]
  18. The different faces of poly(ethylene glycol) [Link]
PubChem Substance
347911107
RxNav
8514
MSDS
Download (229 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableDry Eyes2
4CompletedNot AvailableMyopia1
4CompletedBasic ScienceDry Eyes1
4CompletedTreatmentDry Eye Due to Sjögren's Syndrome1
4CompletedTreatmentDry Eye Syndrome (DES)5
4CompletedTreatmentDry Eye Syndrome (DES) / Dry Eyes1
4CompletedTreatmentDry Eyes4
4CompletedTreatmentDry Eyes / Glaucoma1
4CompletedTreatmentGlaucoma / Ocular Hypertension1
4CompletedTreatmentSeasonal Allergic Conjunctivitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
LiquidOphthalmic
Solution / dropsOphthalmic2.5 mg/1mL
CreamTopical.3 mg/15mg
Solution, gel forming / dropsOphthalmic
Solution / dropsOphthalmic
SolutionOphthalmic
SolutionConjunctival; Ophthalmic
CreamTopical2.5 mg/50mg
CreamTopical
GelOphthalmic
SolutionOphthalmic; Topical
Solution / dropsOphthalmic10 mg/1mL
LiquidTopical
LiquidOphthalmic1 %
SolutionConjunctival; Topical
Enema
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
boiling point (°C)>250MSDS
water solubility100 % solubleMSDS
Predicted Properties
Not Available
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets
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with our fully connected ADMET & drug target dataset.
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Accelerate your drug discovery research with our ADMET & drug target dataset
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Other
General Function
Zinc ion binding
Specific Function
By generating PPi, plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. PPi inhibits mineralization by binding to nascent hydroxyapat...
Gene Name
ENPP1
Uniprot ID
P22413
Uniprot Name
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
Molecular Weight
104923.58 Da
References
  1. Impact of Surface Polyethylene Glycol (PEG) Density on Biodegradable Nanoparticle Transport in Mucus ex vivo and Distribution in vivo [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Transcription coactivator activity
Specific Function
Oxidoreductase required for tumor suppression. NAPDH-bound form inhibits nuclear import by competing with nuclear import substrates for binding to a subset of nuclear transport receptors. May act a...
Gene Name
HTATIP2
Uniprot ID
Q9BUP3
Uniprot Name
Oxidoreductase HTATIP2
Molecular Weight
27048.765 Da

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Leukotriene-b4 20-monooxygenase activity
Specific Function
Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate, myristate and palmitate. Has little activity toward prostaglandins A1 and E1. Oxidizes arachidonic acid to 2...
Gene Name
CYP4A11
Uniprot ID
Q02928
Uniprot Name
Cytochrome P450 4A11
Molecular Weight
59347.31 Da
References
  1. PEGylated Proteins: Evaluation of Their Safety in the Absence of Definitive Metabolism Studies [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Zinc ion binding
Specific Function
Class-III ADH is remarkably ineffective in oxidizing ethanol, but it readily catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione.
Gene Name
ADH5
Uniprot ID
P11766
Uniprot Name
Alcohol dehydrogenase class-3
Molecular Weight
39723.945 Da
References
  1. PEGylated Proteins: Evaluation of Their Safety in the Absence of Definitive Metabolism Studies [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sulfotransferase activity
Specific Function
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of catecholamines, phenolic drugs and neurotransmitters. Has also estroge...
Gene Name
SULT1A1
Uniprot ID
P50225
Uniprot Name
Sulfotransferase 1A1
Molecular Weight
34165.13 Da
References
  1. PEGylated Proteins: Evaluation of Their Safety in the Absence of Definitive Metabolism Studies [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Johnson BM, Charman WN, Porter CJ: An in vitro examination of the impact of polyethylene glycol 400, Pluronic P85, and vitamin E d-alpha-tocopheryl polyethylene glycol 1000 succinate on P-glycoprotein efflux and enterocyte-based metabolism in excised rat intestine. AAPS PharmSci. 2002;4(4):E40. doi: 10.1208/ps040440. [Article]

Drug created on December 03, 2015 16:51 / Updated on July 29, 2021 06:27