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Macrogol is the international nonproprietary name for polyethylene glycol (PEG) used in medicine. Macrogols are commonly used as laxatives, i.e. to treat constipation, in both children and adults.

Lower molecular weight macrogols are used as excipients in pharmaceutical products as solvents in oral liquids and soft capsules. Solid variants are used as ointment bases, tablet bindings, film coatings and lubricants.

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.

Popular types include:

  • macrogol 3350
  • macrogol 4000
  • macrogol 6000

The number represents the average molecular mass. Combining different molecular masses provides some control over the consistency.


Video Macrogol



Medical uses

Laxative

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.

A 2007 comparison showed that patients suffering from constipation had a better response to macrogol than to tegaserod.

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

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.

Other

Macrogol is also commonly used to fuse B-cells with myeloma cells in monoclonal antibody production.


Maps Macrogol



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.


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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. With excessive use, it can cause diarrhea.


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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.


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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.


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Chemistry


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Available forms

Macrogol is sold as non-prescription preparation in powder form. 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 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 and is swallowed. 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.


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Research

Nerves and spinal cords
  • 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.
  • 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. When coupled with melatonin, 75% of damaged sciatic nerves were rendered viable.
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.
  • 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.
Other
  • Macrogol, when labeled with a near-infrared fluorophore, has been used in preclinical work as a vascular agent, lymphatic agent, and general tumor-imaging agent by exploiting the enhanced permeability and retention effect (EPR) of tumors.

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References

Source of the article : Wikipedia

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