Macrogol is theinternational nonproprietary name used forpolyethylene glycol (PEG) as a medication ingredient.[3] It is usually followed by a number indicating the averagemolecular weight, indicating the length of the polymer of the specific molecule in use.[3] Macrogol is used as alaxative to treatconstipation in children and adults.[4] It is takenby mouth.[4] Benefits usually occur within three days.[5] It is also used as anexcipient.[6] It is also used to clear thebowels before acolonoscopy,[4] when the onset of the laxative effect is more rapid, typically within an hour.[7]
Macrogol came into use as a bowel prep in 1980 and was approved for medical use in the United States in 1999.[11][12][13] It is available as ageneric medication andover the counter.[4][14] In 2023, it was the 196th most commonly prescribed medication in the United States, with more than 2million prescriptions.[15][16] It is also formulated together withelectrolytes.[17] In 2023, the combination with electrolytes was the 273rd most commonly prescribed medication in the United States, with more than 800,000 prescriptions.[15][18]
In those with chronic constipation it works better thanlactulose.[20]
Popular types include: macrogol 3350,[21] macrogol 4000, and macrogol 6000.[22] The number represents themolecular weight.[3] Combining different molecular weights provides some control over the consistency.[23]
Macrogol is used as anexcipient in pharmaceutical products.[6] Lower-molecular-weight variants are used as solvents in oral liquids and softcapsules, whereas solid variants are used asointment bases,tablet binders,film coatings, andlubricants.[23]
The doses of macrogol as anexcipient are too low to have relevant contraindications.[28]
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.[29]
Oral macrogol is generally well tolerated. Possible side effects include headache, bloating, nausea,allergies, andelectrolyte imbalance, mainlyhypokalaemia (low bloodpotassium levels) andhyperkalaemia (high blood potassium levels). Hyperkalaemia is not an effect of macrogol itself but of potassium salts which are usually part of macrogol formulations.[19]
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. Forantiepileptic drugs, such a mechanism has been described in rare cases.[19]
Macrogol is an osmotically acting laxative; that is, an inert substance that passes through thegut without being absorbed into the body. It relievesconstipation 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 thestools in the bowel, making them softer and easier to pass, as well as improvinggut motility.[19][30][31]
When sold for gut cleansing (and as a laxative), it is usually in combination with salts such assodium bicarbonate,sodium chloride andpotassium chloride[32] to help mitigate the possibility of electrolyte imbalance anddehydration. Brand names include Cosmocol, Cololyt, Glycoprep, Laxido, Miralax, Molaxole, Movicol, and Osmolax.
Polyethylene glycol-electrolyte solution is afixed-dose combination medication sold under various brand names in the US, including Colyte,[33] Gavilyte, Golytely,[34] Nulytely,[35] Moviprep,[36] and Trilyte.[37][38] Brand names available in the UK include Cosmocol, Klean-Prep, Laxido, Molaxole, Movicol, Plenvu,[1] Transisoft, and Vistaprep.[39] As of June 2023[update], 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.[40] It isindicated for cleansing of the colon in preparation for colonoscopy in adults.[40]
The proteinuricase can bePEGylated to formpegloticase, which improves its solubility at physiologicalpH, increases serum half-life and reduces immunogenicity without compromising activity. Upper images show the wholetetramer, lower images show one of the lysines that is PEGylated. (PDB:1uox PEG-uricase model from reference[41])
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 reducestoxicity, and it allows for longer dosing intervals. It also reduces the proteins' immunogenicity. Examples for PEGylated proteins includepeginterferon alfa-2a and-2b, which are used to treathepatitis C,pegfilgrastim, which is used to treatneutropenia, andpegloticase for the treatment ofgout.[19]
There is evidence demonstrating PEG-induced repair of specific nerve cells in animal models:
It has been shown that macrogol can improve healing ofspinal injuries in dogs.[42]
One of the earlier findings is that macrogol can aid in nerve repair inearthworms.[43]
The subcutaneous injection of macrogol 2000 in guinea pigs after spinal cord injury leads to rapid recovery through molecular repair of nerve membranes.[44] The effectiveness of this treatment to preventparaplegia in humans after an accident is not known yet.
Macrogol is being used in the repair of motor neurons damaged in crush or laceration incidentsin vivo andin vitro in rats. When coupled with melatonin, 75% of damaged sciatic nerves were rendered viable.[45]
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 inclinical trials.[47]
^Mahmoud NN, Bleier JI, Aarons CB, Paulson EC, Shangmugan S, Fry RD (2016)."Colon and Rectum". In Townsend CM, Beauchamp RD, Evers BM, Mattox KL (eds.).Sabiston Textbook of Surgery E-Book: The Biological Basis of Modern Surgical Practice. Elsevier Health Sciences. p. 1325.ISBN978-0-323-40163-0.
^Aronson JK (2015)."Glycols".Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. Elsevier. p. 567.ISBN978-0-444-53716-4.
^abcdefHaberfeld, ed. (2015).Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
^Lee-Robichaud H, Thomas K, Morgan J, Nelson RL (July 2010). "Lactulose versus Polyethylene Glycol for Chronic Constipation".The Cochrane Database of Systematic Reviews (7) CD007570.doi:10.1002/14651858.CD007570.pub2.PMID20614462.
^Hardikar W, Cranswick N, Heine RG (2007). "Macrogol 3350 plus electrolytes for chronic constipation in children: a single-centre, open-label study".Journal of Paediatrics and Child Health.43 (7–8):527–531.doi:10.1111/j.1440-1754.2007.01116.x.PMID17635680.S2CID42699177.
^Veronese FM, Harris JM (June 2002). "Introduction and overview of peptide and protein pegylation".Advanced Drug Delivery Reviews.54 (4):453–456.doi:10.1016/S0169-409X(02)00020-0.PMID12052707.
^Wenande E, Garvey LH (July 2016). "Immediate-type hypersensitivity to polyethylene glycols: a review".Clinical and Experimental Allergy.46 (7):907–922.doi:10.1111/cea.12760.PMID27196817.S2CID1247758.
^Mutschler E (2013).Arzneimittelwirkungen (in German) (10 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 608.ISBN978-3-8047-2898-1.
^Chaussade S (November 1999). "Mechanisms of action of low doses of polyethylene glycol in the treatment of functional constipation".Italian Journal of Gastroenterology and Hepatology.31 (Suppl 3):S242–S244.PMID10726227.
^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.PMID17826865.
^Borgens RB, Bohnert D (December 2001). "Rapid recovery from spinal cord injury after subcutaneously administered polyethylene glycol".Journal of Neuroscience Research.66 (6):1179–1186.doi:10.1002/jnr.1254.PMID11746451.S2CID11902183.
^Stavisky RC, Britt JM, Zuzek A, Truong E, Bittner GD (March 2005). "Melatonin enhances the in vitro and in vivo repair of severed rat sciatic axons".Neuroscience Letters.376 (2):98–101.doi:10.1016/j.neulet.2004.11.033.PMID15698928.S2CID24634247.
^Corpet DE, Parnaud G, Delverdier M, Peiffer G, Taché S (June 2000). "Consistent and fast inhibition of colon carcinogenesis by polyethylene glycol in mice and rats given various carcinogens".Cancer Research.60 (12):3160–3164.PMID10866305.
Clinical trial numberNCT04446299 for "Study 301: BLI4900 Versus an FDA-approved Comparator in Adult Subjects Prior to Colonoscopy" atClinicalTrials.gov
Clinical trial numberNCT04446312 for "Study 302: BLI4900 Versus an FDA-approved Comparator in Adult Subjects Prior to Colonoscopy" atClinicalTrials.gov
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