Macrogol

For non-medical uses of this substance, see Polyethylene glycol.

Macrogol
Clinical data
Trade namesMiraLax, ClearLax, Golytely, others
Other namesPolyethylene glycol (PEG), PEG 3350, PEG 4000, PEG 6000
AHFS/Drugs.comProfessional Drug Facts
MedlinePlusa603032
License data
Pregnancy
category
  • AU: B1
Routes of
administration		By mouth
Drug classOsmotic laxative
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityNone
ExcretionFeces (100%)
Identifiers
  • Poly(oxyethylene)
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaH–(OCH2CH2)n–OH
 ☒NcheckY (what is this?)  (verify)

Macrogol, also called polyethylene glycol (PEG), is used as a laxative to treat constipation in children and adults.[1] It is taken by mouth.[1] Benefits usually occur within three days.[2] Generally it is only recommended for up to two weeks.[3] It is also used as an excipient.[4] It is also used to clear the bowels (bowel prep) before a colonoscopy,[1] when the onset of the laxative effect is more rapid, typically within an hour.[5]

Side effects may include increased bowel gas, abdominal pain, and nausea.[1] Rare but serious side effects may include an abnormal heartbeat, seizures, and kidney problems.[6] Use appears to be safe during pregnancy.[7][1] It is classified as an osmotic laxative:[2] It works by increasing the amount of water in the stool.[3]

Macrogol came into use as a bowel prep in 1980 and was approved for medical use in the United States in 1999.[8][9][10] It is available as a generic medication and over the counter.[1][11] In 2022, it was the 209th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[12][13] It is also formulated together with electrolytes.[14] In 2022, the combination with electrolytes was the 282nd most commonly prescribed medication in the US, with more than 600,000 prescriptions.[12][15]

Medical uses

A polyethylene glycol (PEG) and electrolytes solution used as a laxative used to cleanse the colon before colonoscopy, lower gastrointestinal series, or colon surgery.

Constipation

Macrogol 4000, pharmaceutical quality

Macrogol 3350, often in combination with electrolytes, is used for short-term relief of constipation as well as for long-term use in constipation of various causes, including in multiple sclerosis and Parkinson's disease patients (an often-overlooked non-motor symptom) as well as constipation caused by pharmaceutical drugs such as opioids and anticholinergics. Whole bowel irrigation with macrogol is part of the bowel preparation before surgery or colonoscopy. Limited data also support its use for the treatment of fecal impaction.[16]

In those with chronic constipation it works better than lactulose.[17]

A 2007 comparison showed that people with constipation had a better response to macrogol than to tegaserod.[18] Popular types include: macrogol 3350,[19] macrogol 4000, and macrogol 6000.[20] The number represents the average molecular mass.[citation needed] Combining different molecular masses provides some control over the consistency.[21]

Excipient

Macrogol is used as an excipient in pharmaceutical products.[4] Lower-molecular-weight variants are used as solvents in oral liquids and soft capsules, whereas solid variants are used as ointment bases, tablet binders, film coatings, and lubricants.[21]

For example, PEG-2000 is one of the excipients in the Moderna COVID-19 vaccine.[22][23]

PEGylation

Macrogols are also attached to biopharmaceutical drugs to slow down their degradation in the human body and increase their duration of action, as well as to reduce immunogenicity. This process is called PEGylation.[24][25]

Contraindications

Contraindications for macrogol taken orally as a laxative are intestinal perforation, bowel obstruction, ileus, inflammatory bowel diseases, and toxic megacolon.[16]

The doses of macrogol as an excipient are too low to have relevant contraindications.[26]

Allergy to macrogol is rare, and usually appears as an allergy to an increasing number of seemingly unrelated products, including cosmetics, drugs that use it as an excipient, and peri-procedural substances such as ultrasound gel.[27]

Adverse effects

Oral macrogol is generally well tolerated. Possible side effects include headache, bloating, nausea, allergies, and electrolyte imbalance, mainly hypokalaemia (low blood potassium levels) and hyperkalaemia (high blood potassium levels). Hyperkalaemia is not an effect of macrogol itself but of potassium salts which are usually part of macrogol formulations.[16] With excessive use, it can cause diarrhea.

Interactions

The interaction potential is low. Absorption of other pharmaceutical drugs can be reduced because oral macrogol accelerates intestinal passage, but this is seldom clinically relevant. For antiepileptic drugs, such a mechanism has been described in rare cases.[16]

Pharmacology

Mechanism of action as a laxative

Macrogol is an osmotically acting laxative; that is, an inert substance that passes through the gut without being absorbed into the body. It relieves constipation because it causes water to be retained in the bowel instead of being absorbed into the body. This increases the water content and volume of the stools in the bowel, making them softer and easier to pass, as well as improving gut motility.[16][28][29]

Chemistry

Main article: Polyethylene glycol
For the synthesis of macrogol, see Polyethylene glycol § Production.

Available forms

When sold for gut cleansing (and as a laxative), it is usually in combination with salts such as sodium bicarbonate, sodium chloride and potassium chloride[30] to help mitigate the possibility of electrolyte imbalance and dehydration. Brand names include CosmoCol, Cololyt, Glycoprep, Laxido, MiraLax, Molaxole, Movicol, and Osmolax.

Polyethylene glycol-electrolyte solution is a fixed-dose combination medication sold under various brand names in the US, including Colyte,[31] Gavilyte, Golytely,[32] Nulytely,[33] Moviprep,[34] and Trilyte.[35][36] Brand names available in the UK include CosmoCol, Klean-Prep, Laxido, Molaxole, Movicol, Plenvu, TransiSoft, and VistaPrep.[37] As of June 2023, polyethylene glycol 3350 is available in the US as a combination with sodium sulfate, potassium chloride, magnesium sulfate, and sodium chloride and sold under the brand name Suflave.[38] It is indicated for cleansing of the colon in preparation for colonoscopy in adults.[38]

Research

PEGylation

The protein uricase can be PEGylated to form pegloticase, which improves its solubility at physiological pH, increases serum half-life and reduces immunogenicity without compromising activity. Upper images show the whole tetramer, lower images show one of the lysines that is PEGylated. (PDB: 1uox​ PEG-uricase model from reference[39])
Main article: PEGylation

When attached to various biopharmaceutical medications (which are proteins), macrogol results in a slowed clearance of the carried protein from the blood. This makes for a longer-acting medicinal effect and reduces toxicity, and it allows for longer dosing intervals. It also reduces the proteins' immunogenicity. Examples for PEGylated proteins include peginterferon alfa-2a and -2b, which are used to treat hepatitis C, pegfilgrastim, which is used to treat neutropenia, and pegloticase for the treatment of gout.[16]

Nerves and spinal cords

There is evidence demonstrating PEG-induced repair of specific nerve cells in animal models:

  • It has been shown that macrogol can improve healing of spinal injuries in dogs.[40]
  • One of the earlier findings is that macrogol can aid in nerve repair in earthworms.[41]
  • The subcutaneous injection of macrogol 2000 in guinea pigs after spinal cord injury leads to rapid recovery through molecular repair of nerve membranes.[42] The effectiveness of this treatment to prevent paraplegia in humans after an accident is not known yet.
  • Macrogol is being used in the repair of motor neurons damaged in crush or laceration incidents in vivo and in vitro in rats. When coupled with melatonin, 75% of damaged sciatic nerves were rendered viable.[43]

Cancer prevention

  • High-molecular-weight macrogol (e.g., 8000 g/mol) has been shown to be a dietary preventive agent against colorectal cancer in animal models.[44][medical citation needed]
  • The Chemoprevention Database shows macrogol is the most effective known agent for the suppression of chemical carcinogenesis in rats. Cancer prevention applications in humans, however, have not yet been tested in clinical trials.[45]

Other

References

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  2. ^ a b "DailyMed - polyethylene glycol 3350 powder, for solution". dailymed.nlm.nih.gov. Archived from the original on 26 April 2021. Retrieved 19 April 2019.
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  4. ^ a b "Macrogol as Excipient". Biesterfeld AG. Retrieved 10 June 2022.
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  39. ^ Sherman MR, Saifer MG, Perez-Ruiz F (January 2008). "PEG-uricase in the management of treatment-resistant gout and hyperuricemia". Advanced Drug Delivery Reviews. 60 (1): 59–68. doi:10.1016/j.addr.2007.06.011. PMID 17826865.
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  • Clinical trial number NCT04446299 for "Study 301: BLI4900 Versus an FDA-approved Comparator in Adult Subjects Prior to Colonoscopy" at ClinicalTrials.gov
  • Clinical trial number NCT04446312 for "Study 302: BLI4900 Versus an FDA-approved Comparator in Adult Subjects Prior to Colonoscopy" at ClinicalTrials.gov

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Church in Copenhagen, DenmarkGodthaab Church, CopenhagenGodthaab Church55°41′1.5″N 12°31′33.5″E / 55.683750°N 12.525972°E / 55.683750; 12.525972Location51A NyelandsvejFrederiksberg, CopenhagenCountryDenmarkDenominationChurch of DenmarkWebsitewww.godthaabskirken.dkHistoryStatusChurchArchitectureArchitect(s)Gotfred TvedeArchitectural typeChurchStyleNeo-BaroqueGroundbreaking2 October 1909Completed19 March 1911SpecificationsMaterialsBrickAdministrationArchdioce...

Holger Mann

German politician Holger MannMember of the BundestagIncumbentAssumed office 2021 Personal detailsBorn (1979-02-19) 19 February 1979 (age 45)Dresden, East Germany(now Germany)Political partySPD Holger Mann (born 19 February 1979) is a German politician of the Social Democratic Party (SPD) who has been serving as a member of the Bundestag since 2021.[1] Early life and education Mann was born 1979 in the East German city of Dresden and studied history.[2] He moved to Lei...

 

 

Nicole Johnson (monster truck driver)

American professional monster truck driver Nicole Michelle Johnson redirects here. For the beauty queen named Nicole Michele Johnson, see Nicole Johnson (Miss California USA). Nicole JohnsonPersonal informationBirth nameNicole Michelle JardinNationalityAmericanBorn (1974-01-16) January 16, 1974 (age 50)Ventura County, California, U.S.Alma materBrigham Young UniversitySpouseFrank JohnsonSportCountryUnited StatesSportMonster JamTeamScooby-DooRetired2017 Nicole Michelle Johnson (b...