Colchicine Pharmacokinetics and Mechanism of Action

Abstract

Colchicine is a tricyclic, lipid-soluble alkaloid derived from the plant of the Lily family Colchicum autumnale, sometimes called the "autumn crocus". It is predominantly metabolized in the gastrointestinal tract. Two proteins, P-glycoprotein (P-gp) and CYP3A4 seem to play a pivotal role, governing its pharmacokinetic. The commonest side effects are gastrointestinal (nausea, vomiting and particularly dose-related-diarrhea) occurring in 5-10% of patients. Colchicine exerts its unique action mainly through inhibition of microtubule polymerization. Microtubule polymerization affects a variety of cellular processes including maintenance of shape, signaling, division, migration, and cellular transport. Colchicine interferes with several inflammatory pathways including adhesion and recruitment of neutrophils, superoxide production, inflammasome activation, the RhoA/Rho effector kinase (ROCK) pathway and the tumor necrosis factor alpha (TNF-α) -induced nuclear factor κΒ (NF-κΒ) pathway attenuating the inflammatory response. This concise paper attempts to give a brief review of its pharmacokinetic properties and its main mechanisms of action.

The Role of Colchicine in Treating Postoperative and Post-catheter Ablation Atrial Fibrillation

“…Colchicine is easily absorbed after oral administration. 28 Peak concentration is reached in 0.5 to 2 hours, and the plasma t 1/2 is~20 minutes. In contrast, the t 1/2 in leukocytes is estimated to be~60 hours.…”

Targeting P-Glycoprotein: Nelfinavir Reverses Adriamycin Resistance in K562/ADR Cells

“…2, Table 2). It is well known that colchicine, paclitaxel, and imatinib are all substrates for P-gp, and cisplatin is neither an inhibitor nor a substrate of P-gp [32][33][34][35]. NFV can selectively reverse the resistance of drugs transported by P-gp; for the non-P-gp substrate drug cisplatin, NFV does not radically change its drug resistance (Fig.…”

Prophylaxis of Acute Arthritis at Initiation of Urate-Lowering Therapy in Gout Patients

“…Tolerance to colchicine is dose-dependent and the recommended dose for prophylaxis of arthritis (0.6 mg once or twice a day), as a rule, is better tolerable than higher doses used earlier to treat acute gout arthritis (1.2 mg at acute flare with subsequent increase by 0.6 mg hourly) [25]. The most common colchicine-induced adverse drug reactions occur with the gastrointestinal tract, namely nausea and diarrhea, which are reported by 5-10% of the patients, even in cases of low-dose colchicine [26]. Gastrotoxicity is highly likely to depend on the dose and can be reduced by decreasing the dose of colchicine.…”