Colchicine is used chiefly in the treatment of gout but is also valuable in other inflammatory diseases such as familial Mediterranean fever (FMF). Three proteins play pivotal roles in colchicine pharmacokinetics: the colchicine receptor, tubulin, which governs the plasma elimination half-life of the drug; intestinal and hepatic CYP3A4, which is key to the biotransformation of colchicine; and P-glycoprotein, a cell efflux pump that regulates the tissue distribution of colchicine, as well as its excretion via the biliary tract and kidneys. Pharmacokinetic studies have been performed using a radioimmunology assay to measure blood colchicine levels. Absorption after oral ingestion varies widely (from 24% to 88% of the dose), the volume of distribution is extremely large (7 l/kg), and binding to albumin is moderate. Colchicine is excreted chiefly through the liver and has an elimination half-life of 20-40 hours. With repeated doses of about 1mg/day, the steady-state is achieved within 8 days and concentrations range from 0.3 to 2.5 ng/ml. Studies of associations between pharmacokinetic parameters and pharmacodynamics show that effects are correlated, not to plasma levels, but to levels in leukocytes. Adverse events are not uncommon, most notably when colchicine is used in combination with drugs that interact with CYP3A4 and/or P-glycoprotein, thereby decreasing the renal and/or hepatic elimination of colchicine. Careful monitoring in this situation is effective in preventing the development of toxicity.