Macrogol

File:GaviLyte G.jpg solution used as a laxative used to cleanse the colon before colonoscopy, lower gastrointestinal series, or colon surgery.]]

File:Polyethylene glycol 4000.jpg

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 people with multiple sclerosis or Parkinson's disease as well as constipation caused by pharmaceutical drugs such as opioids and anticholinergics.{{medcn|date=April 2025}} Whole bowel irrigation with macrogol is part of the bowel preparation before surgery or colonoscopy.{{medcn|date=April 2025}} Limited data also support its use for the treatment of fecal impaction.

In those with chronic constipation it works better than lactulose.{{cite journal | vauthors = Lee-Robichaud H, Thomas K, Morgan J, Nelson RL | title = Lactulose versus Polyethylene Glycol for Chronic Constipation | journal = The Cochrane Database of Systematic Reviews | issue = 7 | pages = CD007570 | date = July 2010 | pmid = 20614462 | doi = 10.1002/14651858.CD007570.pub2 }}

Popular types include: macrogol 3350, macrogol 4000, and macrogol 6000. The number represents the molecular weight. Combining different molecular weights provides some control over the consistency.

Macrogol is used as an excipient in pharmaceutical products. 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.

For example, PEG-2000 is one of the excipients in the Moderna COVID-19 vaccine.{{cite web | url=https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/downloads/standing-orders.pdf | title=Pfizer–BioNTech COVID-19 Vaccine Standing Orders for Administering Vaccine to Persons 12 Years of Age and Older | publisher=Centers for Disease Control and Prevention (CDC) | access-date=5 March 2021 | archive-date=2 March 2021 | archive-url=https://web.archive.org/web/20210302001413/https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/downloads/standing-orders.pdf | url-status=live }}{{cite web |title=What Ingredients are in the COVID-19 Vaccine? |url=https://portal.ct.gov/-/media/DDS/COVID-19_2021/DPH_covidvaccine_ingredients_and_work_2_3_21.pdf |publisher=Connecticut Department of Public Health |access-date=11 July 2021 |archive-date=7 July 2021 |archive-url=https://web.archive.org/web/20210707232909/https://portal.ct.gov/-/media/DDS/COVID-19_2021/DPH_covidvaccine_ingredients_and_work_2_3_21.pdf |url-status=live }}

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.{{Cite journal| vauthors = Porfiryeva NN, Moustafine RI, Khutoryanskiy VV |date=1 January 2020|title=PEGylated Systems in Pharmaceutics|url=https://doi.org/10.1134/S181123822001004X|journal=Polymer Science, Series C|volume=62|issue=1|pages=62–74|doi=10.1134/S181123822001004X|s2cid=226664780 |issn=1555-614X}}

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

The doses of macrogol as an excipient are too low to have relevant contraindications.{{Cite web|url=https://www.medicines.org.uk/emc/product/4482/smpc|title=Compound Macrogol Oral Powder Sugar Free |website=Electronic medicines compendium (emc) |access-date=10 January 2020|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828154130/https://www.medicines.org.uk/emc/product/4482/smpc|url-status=live}}

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.{{cite journal | vauthors = Wenande E, Garvey LH | title = Immediate-type hypersensitivity to polyethylene glycols: a review | journal = Clinical and Experimental Allergy | volume = 46 | issue = 7 | pages = 907–922 | date = July 2016 | pmid = 27196817 | doi = 10.1111/cea.12760 | s2cid = 1247758 }}

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.

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.

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.

{{Main|Polyethylene glycol}}

{{For|the synthesis of macrogol|Polyethylene glycol#Production}}

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[eg. Laxido package insert] 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,{{cite web | title = Colyte- peg-3350 and lectrolytes powder, for solution | author = Meda Pharmaceuticals | url = https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=471296 | work = dailymed | publisher = U.S. National Library of Medicine | date = February 2019}} Gavilyte, Golytely,{{cite web | title=Golytely- polyethylene glycol 3350, sodium sulfate anhydrous, sodium bicarbonate, sodium chloride, potassium chloride powder, for solution | website=DailyMed | date=28 May 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57d22b0b-1ae0-4203-babc-f3bac17bd1c9 | access-date=17 June 2023 | archive-date=31 March 2023 | archive-url=https://web.archive.org/web/20230331093120/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57d22b0b-1ae0-4203-babc-f3bac17bd1c9 | url-status=live }} Nulytely,{{cite web | title=Nulytely- polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride powder, for solution | website=DailyMed | date=16 June 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e7cf708c-937e-4aae-ab0a-0361c144a256 | access-date=17 June 2023 }} Moviprep,{{cite web | title=Moviprep- polyethylene glycol 3350, sodium sulfate, sodium chloride, potassium chloride, ascorbic acid, sodium ascorbate kit | website=DailyMed | date=15 April 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8ff46193-2a3b-4de0-9572-775dda8cd8b2 | access-date=17 June 2023 | archive-date=3 February 2023 | archive-url=https://web.archive.org/web/20230203145935/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8ff46193-2a3b-4de0-9572-775dda8cd8b2 | url-status=live }} and Trilyte.{{cite web | title=Trilyte (polyethylene glycol 3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution) with flavor packs Initial U.S. Approval: 1991 | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=584620 | access-date=17 June 2023 }}{{cite web | title=Polyethylene Glycol-Electrolyte Solution (Professional Patient Advice) | website=Drugs.com | date=20 February 2020 | url=https://www.drugs.com/ppa/polyethylene-glycol-electrolyte-solution.html | access-date=8 June 2020 | archive-date=8 June 2020 | archive-url=https://web.archive.org/web/20200608230354/https://www.drugs.com/ppa/polyethylene-glycol-electrolyte-solution.html | url-status=live }} Brand names available in the UK include Cosmocol, Klean-Prep, Laxido, Molaxole, Movicol, Plenvu,{{cite web | title=Regulatory Decision Summary for Plenvu | website=Drug and Health Products Portal | date=16 August 2024 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/RDS1732551487982 | access-date=27 December 2024}} Transisoft, and Vistaprep.{{cite web | website=mims.co.uk | title=Search or browse MIMS | url=https://www.mims.co.uk/search/drugs?keywords=Macrogol | access-date=24 April 2023 | archive-date=24 April 2023 | archive-url=https://web.archive.org/web/20230424072604/https://www.mims.co.uk/search/drugs?keywords=Macrogol | url-status=unfit }} {{Asof|2023|June}}, 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.{{cite web | title = Suflave (polyethylene glycol 3350, sodium sulfate, potassium chloride, magnesium sulfate, and sodium chloride for oral solution) | work = Braintree Laboratories, Inc. | publisher = U.S. Food and Drug Administration | date = June 2023 | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215344s000lbl.pdf| archive-url = https://web.archive.org/web/20230617064156/https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215344s000lbl.pdf| url-status = dead| archive-date = 17 June 2023}} It is indicated for cleansing of the colon in preparation for colonoscopy in adults.

File:PegUricase.png 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)]]

{{main|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.

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.
• One of the earlier findings is that macrogol can aid in nerve repair in earthworms.
• The subcutaneous injection of macrogol 2000 in guinea pigs after spinal cord injury leads to rapid recovery through molecular repair of nerve membranes. 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.

• High-molecular-weight macrogol (e.g., 8000 g/mol) has been shown to be a dietary preventive agent against colorectal cancer in animal models.{{Medical citation needed|date=September 2021}}
• 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.

• Macrogol is also used to fuse B-cells with myeloma cells in monoclonal antibody production.{{cite journal | vauthors = Lo MM, Tsong TY, Conrad MK, Strittmatter SM, Hester LD, Snyder SH | title = Monoclonal antibody production by receptor-mediated electrically induced cell fusion | journal = Nature | volume = 310 | issue = 5980 | pages = 792–794 | year = 1984 | pmid = 6088990 | doi = 10.1038/310792a0 | bibcode = 1984Natur.310..792L | s2cid = 4357934 }}

{{reflist|refs=

{{cite book|title=Austria-Codex|editor=Haberfeld|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2015|language=de}}

{{cite journal | vauthors = Veronese FM, Harris JM | title = Introduction and overview of peptide and protein pegylation | journal = Advanced Drug Delivery Reviews | volume = 54 | issue = 4 | pages = 453–456 | date = June 2002 | pmid = 12052707 | doi = 10.1016/S0169-409X(02)00020-0}}

{{Cite book | isbn = 9780849335853 | page = 287 | vauthors = Smolinske SC | title = Handbook of Food, Drug, and Cosmetic Excipients | year = 1992 | publisher = CRC Press}}

{{cite journal | vauthors = Hardikar W, Cranswick N, Heine RG | title = Macrogol 3350 plus electrolytes for chronic constipation in children: a single-centre, open-label study | journal = Journal of Paediatrics and Child Health | volume = 43 | issue = 7–8 | pages = 527–531 | year = 2007 | pmid = 17635680 | doi = 10.1111/j.1440-1754.2007.01116.x | s2cid = 42699177}}

{{cite journal | vauthors = Hyry H, Vuorio A, Varjonen E, Skyttä J, Mäkinen-Kiljunen S | title = Two cases of anaphylaxis to macrogol 6000 after ingestion of drug tablets | journal = Allergy | volume = 61 | issue = 8 | pages = 1021 | date = August 2006 | pmid = 16867059 | doi = 10.1111/j.1398-9995.2006.01083.x | s2cid = 36543393}}

{{Cite book| vauthors = Mutschler E |title=Arzneimittelwirkungen|language=de|location=Stuttgart|publisher=Wissenschaftliche Verlagsgesellschaft|year=2013|edition=10|page=608|isbn=978-3-8047-2898-1}}

{{cite journal | vauthors = Corpet DE, Parnaud G, Delverdier M, Peiffer G, Taché S | title = Consistent and fast inhibition of colon carcinogenesis by polyethylene glycol in mice and rats given various carcinogens | journal = Cancer Research | volume = 60 | issue = 12 | pages = 3160–3164 | date = June 2000 | pmid = 10866305}}

{{cite web | url = http://www.inra.fr/internet/Projets/reseau-nacre/sci-memb/corpet/indexan.html | work = Chemoprevention Database | title = Chemoprevention of Colorectal Cancer | archive-url = https://web.archive.org/web/20051123121321/http://www.inra.fr/Internet/Projets/reseau-nacre/sci-memb/corpet/indexan.html | archive-date = 23 November 2005 | via = Inra.fr | access-date = 30 November 2012}}

{{cite journal | vauthors = Borgens RB, Bohnert D | title = Rapid recovery from spinal cord injury after subcutaneously administered polyethylene glycol | journal = Journal of Neuroscience Research | volume = 66 | issue = 6 | pages = 1179–1186 | date = December 2001 | pmid = 11746451 | doi = 10.1002/jnr.1254 | s2cid = 11902183}}

{{cite journal | vauthors = Stavisky RC, Britt JM, Zuzek A, Truong E, Bittner GD | title = Melatonin enhances the in vitro and in vivo repair of severed rat sciatic axons | journal = Neuroscience Letters | volume = 376 | issue = 2 | pages = 98–101 | date = March 2005 | pmid = 15698928 | doi = 10.1016/j.neulet.2004.11.033 | s2cid = 24634247}}

{{cite journal | vauthors = Sherman MR, Saifer MG, Perez-Ruiz F | title = PEG-uricase in the management of treatment-resistant gout and hyperuricemia | journal = Advanced Drug Delivery Reviews | volume = 60 | issue = 1 | pages = 59–68 | date = January 2008 | pmid = 17826865 | doi = 10.1016/j.addr.2007.06.011}}

{{cite news|url = http://www.seattlepi.com/health/202292_spinal04.html|date = 4 December 2004|title = Study on dogs yields hope in human paralysis treatment|author = Bowman, Lee|publisher = seattlepi.com|access-date = 26 June 2016|archive-date = 22 September 2021|archive-url = https://web.archive.org/web/20210922030733/https://www.seattlepi.com/lifestyle/health/article/Study-on-dogs-yields-hope-in-human-paralysis-1161183.php|url-status = live}}

{{cite journal | vauthors = Krause TL, Bittner GD | title = Rapid morphological fusion of severed myelinated axons by polyethylene glycol | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 4 | pages = 1471–1475 | date = February 1990 | pmid = 2304913 | pmc = 53497 | doi = 10.1073/pnas.87.4.1471 | doi-access = free | bibcode = 1990PNAS...87.1471K}}

{{cite journal | vauthors = Chaussade S | title = Mechanisms of action of low doses of polyethylene glycol in the treatment of functional constipation | journal = Italian Journal of Gastroenterology and Hepatology | volume = 31 | issue = Suppl 3 | pages = S242–S244 | date = November 1999 | pmid = 10726227}}

}}

• {{ClinicalTrialsGov|NCT04446299|Study 301: BLI4900 Versus an FDA-approved Comparator in Adult Subjects Prior to Colonoscopy}}
• {{ClinicalTrialsGov|NCT04446312|Study 302: BLI4900 Versus an FDA-approved Comparator in Adult Subjects Prior to Colonoscopy}}

{{Laxatives}}

{{Portal bar | Medicine}}

{{Authority control}}

Category:Laxatives

Category:Excipients

Category:Drugs developed by Merck & Co.

Category:Drugs developed by Bayer

Category:Combination drugs

Category:Wikipedia medicine articles ready to translate