Colchicine

Colchicine
ATC Code M04AC01
Formula C22H25NO6
Molar Mass (g·mol−1) 399,43
Physical State solid
Melting Point (°C) 155–157
PKS Value 1.85
CAS Number 64-86-8
PUB Number 6167
Drugbank ID DB01394
Solubility soluble in water

Basics

Colchicine is a drug used to treat gout, Behçet's disease, the treatment of pericarditis and familial Mediterranean fever. It is less preferable to NSAIDs or steroids in the treatment of gout. It is derived from a plant in the lily family known as Colchicum autumnale or autumn crocus. Colchicine is taken orally.

In the form of autumn crocus, the substance was used as early as 1500 BC to treat joint swelling. Colchicine was first isolated in 1820 by the French chemists Pelletier and Caventou. In 1833, the German chemist Philipp Lorenz Geiger also succeeded in isolating the active substance in its pure form, which he subsequently named colchicine. The drug was first officially approved by the FDA in 1961. However, the efficacy of the substance was not truly proven until the early 2000s, when it was re-examined in clinical trials. This was followed by a re-approval and patenting of the substance by the company URL-Pharma.

Pharmacology

Pharmacodynamics

The exact mechanism of action of colchicine is not fully understood, but it likely occurs via downstream inhibition of inflammatory responses caused by disruption of the structural protein tubulin. Colchicine is thought to cause disruption of the inflammasome complex present in both monocytes and neutrophils, which normally leads to activation of interleukin-1, a major mediator of inflammation. In addition to the above effects, colchicine interferes with several signaling pathways, including neutrophil adhesion and recruitment, superoxide production, the RhoA/Rho effector kinase (ROCK) signaling pathway, and the nuclear factor-κΒ (NF-κΒ) signaling pathway, thereby attenuating the inflammatory response.

At the molecular level, colchicine can be described as an antimitotic drug that blocks the mitotic activity of cells in the metaphase of the cell cycle. Specifically, colchicine binds to tubulin and forms complexes that bind to microtubules. This stops their elongation. At low concentrations, colchicine stops microtubule growth; at higher concentrations, colchicine causes microtubule depolymerization, resulting in cell destruction.

Pharmacokinetics

Colchicine is rapidly absorbed from the gastrointestinal tract after oral administration. The bioavailability of colchicine is approximately 45%. Plasma protein binding for colchicine is relatively low at 39%, with the major portion bound to the plamsaprotein albumin. Colchicine is metabolized in the liver and converted by demethylation into the two major metabolites 2-O-demethylcolchicine and 3-O-demethylcolchicine. The enzyme CYP3A4 is mainly involved in this process. Between 40- and 65% of the given dose is excreted unchanged in the urine. A proportion is also excreted biliarily. The average elimination half-life of colchicine is between 26 and 31 hours.

Drug Interactions

Because of its narrow therapeutic range and metabolism by the enzyme CYP3A4, the potential for interactions with colchicine is relatively high. Colchicine also interacts with the P-glycoprotein transporter. Fatal drug interactions have occurred when colchicine was taken with other drugs that inhibit P-glycoprotein and CYP3A4, such as erythromycin or clarithromycin.

People taking macrolide antibiotics, ketoconazole, or cyclosporine, or people with liver or kidney disease should not take colchicine because these drugs and conditions may interfere with colchicine metabolism and increase blood levels. People with HIV/AIDS taking atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, or saquinavir are at greatly increased risk of side effects. Grapefruit juice and statins may also increase blood colchicine concentrations.

Toxicity

Side effects

An overdose of colchicine can cause serious side effects and death.

Typical side effects of moderate doses include:

  • Gastrointestinal symptoms
  • Diarrhea
  • Neutropenia

High doses can also damage bone marrow, cause anemia, and cause hair loss. All of these side effects can be attributed to inhibition of mitosis. Neuromuscular toxicity and rhabdomyolysis may also occur.

Contraindications and precautions

Long-term (prophylactic) use of oral colchicine is absolutely contraindicated in people with advanced renal failure (including dialysis patients). In addition, colchicine should not be used in patentein with hematologic disorders, neutropenia, and severe liver disease.

Whether colchicine is safe during pregnancy is unclear, but use during lactation appears to be safe. Use during pregnancy is not recommended.

Editorial principles

All information used for the content comes from verified sources (recognised institutions, experts, studies by renowned universities). We attach great importance to the qualification of the authors and the scientific background of the information. Thus, we ensure that our research is based on scientific findings.

Markus Falkenstätter

Markus Falkenstätter
Author

Markus Falkenstätter is a writer on pharmaceutical topics in Medikamio's medical editorial team. He is in the last semester of his pharmacy studies at the University of Vienna and loves scientific work in the field of natural sciences.

Mag. pharm Stefanie Lehenauer

Mag. pharm Stefanie Lehenauer
Lector

Stefanie Lehenauer has been a freelance writer for Medikamio since 2020 and studied pharmacy at the University of Vienna. She works as a pharmacist in Vienna and her passion is herbal medicines and their effects.

Your personal medicine assistent

afgis-Qualitätslogo mit Ablauf Jahr/Monat: Mit einem Klick auf das Logo öffnet sich ein neues Bildschirmfenster mit Informationen über Medikamio GmbH & Co KG und sein/ihr Internet-Angebot: medikamio.com/ This website is certified by Health On the Net Foundation. Click to verify.
Drugs

Search our database for drugs, sorted from A-Z with their effects and ingredients.

Substances

All substances with their common uses, chemical components and medical products which contain them.

Diseases

Causes, symptoms and treatment for the most common diseases and injuries.

The contents shown do not replace the original package insert of the medicinal product, especially with regard to dosage and effect of the individual products. We cannot assume any liability for the correctness of the data, as the data was partly converted automatically. A doctor should always be consulted for diagnoses and other health questions. Further information on this topic can be found here.