COLCHICINE - RECENT PHARMACOKINETIC AND CLINICAL PHARMACOLOGICAL DATA

Colchicine is widely used in the treatment of acute goutty arthritis. Recently, colchicine was shown to be effective in inflammatory diseases such as familial Mediterranean fever. Two proteins can modulate its pharmacokinetics: tublin, the specific intracellular receptor for cholchicine which determines the plasma half-life, and P-glycoprotein, an active efflux pump towards some anticancer drugs which regulates colchicine of side effects and the clinical efficacy. Recently, using a specific and sensitive radioimmunoassay, the investigation of plasma concentrations during single and multiple dose studies has allowed to define the colchicine pharmacokinetic parameters. Following oral route, colchicine bioavailability is extremely variable (form 24 to 88% of the administered dose), the distribution volume is elevated (7 J/kg) but the binding to albumin is moderate. Colchicine elimination occured mainly via hepatic pathways and the elimination half-life ranged from 20 to 40 hours. In multiple dose study (1 mg/d), the steady-state is reached 8 days after teh first and administration and plasma concentrations ranged from 0.3 to 2.5 ng/ml. Pharmacokinetic/pharmocodynamic studies show that the biological effects of colchicine were not related to plasma concentrations but with intraleukocyte concentrations. Drug interactions studies show that the biological effects of colchicine were not related to plasma concentrations but with intraleukocyte concentrations. Drug interactions may occur when colchicine is associated to drugs which interact with cytochrome P450 and/or P-glycoprotein and modify renal and/or hepatic clearances. The therapeutic drug monitoring of colchicine during these circumstances could allow tp prevent teh observation of side effects.