Macrogol


Macrogol, also known as polyethylene glycol, is used as a medication to treat constipation in children and adults. It is also used to empty the bowels before a colonoscopy. It is taken by mouth. Benefits usually occur within three days. Generally it is only recommended for up to two weeks.
Side effects may include increased bowel gas, abdominal pain, and nausea. Rare but serious side effects may include an abnormal heartbeat, seizures, and kidney problems. Use appears to be safe during pregnancy. It is classified as an osmotic laxative. It works by increasing the amount of water in the stool.
Macrogol came into use as a bowel prep in 1980 and was approved for medical use in the United States in 1999. It is available as a generic medication and over the counter. In the United Kingdom it costs the NHS about £0.14 per dose as of 2019. In the United States the wholesale cost of this amount is about US$1.40. In 2017, it was the 162nd most commonly prescribed medication in the United States, with more than three million prescriptions. Typically it is formulated together with electrolytes.

Medical uses

Constipation

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 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.
In those with chronic constipation it works better than lactulose.
A 2007 comparison showed that people with constipation had a better response to macrogol than to tegaserod. Popular types include: macrogol 3350, macrogol 4000, and macrogol 6000. The number represents the average molecular mass. Combining different molecular masses provides some control over the consistency.

Excipient

Macrogol is used as an excipient in many 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. It is also used in lubricating eye drops.

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.

Contraindications

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.
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.

Adverse effects

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

Interactions

The interaction potential is low. Resorption 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.

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.

Chemistry

Available forms

Macrogol is sold as a non-prescription preparation in the form of powder. When sold for gut cleansing, it is usually in combination with salts such as sodium bicarbonate, sodium chloride and potassium chloride to help mitigate the possibility of electrolyte imbalance and dehydration. Trade names include SoftLax, Purelax, MiraLax, Laxido, Glycoprep, Movicol, Cololyt and Osmolax, and many others.
It is dissolved in water to create a clear and odorless solution which is then drunk. While most consumers find the taste of macrogol itself to be very mild and unobjectionable, the electrolytes contained in formulations for purging and cleansing give the solution an extremely salty and bitter taste.
Polyethylene glycol-electrolyte solution is a prescription product sold under various brand names including Colyte, Gavilyte, Golytely, Nulytely, Moviprep, and Trilyte.

Research

;PEGylation
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.
When attached to various biopharmaceutical medications, 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.
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