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.
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.
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.