COLCHICINE - RECENT PHARMACOKINETIC AND C LINICAL PHARMACOLOGICAL DATA

Colchicine is widely used in the treatment of acute goutty arthritis. Recently, colchicine was shown to be effective in inflammatory disease s such as familial Mediterranean fever. Two proteins can modulate its pharmacokinetics: tublin, the specific intracellular receptor for chol chicine which determines the plasma half-life, and P-glycoprotein, an active efflux pump towards some anticancer drugs which regulates colch icine of side effects and the clinical efficacy. Recently, using a spe cific and sensitive radioimmunoassay, the investigation of plasma conc entrations during single and multiple dose studies has allowed to defi ne the colchicine pharmacokinetic parameters. Following oral route, co lchicine bioavailability is extremely variable (form 24 to 88% of the administered dose), the distribution volume is elevated (7 J/kg) but t he binding to albumin is moderate. Colchicine elimination occured main ly via hepatic pathways and the elimination half-life ranged from 20 t o 40 hours. In multiple dose study (1 mg/d), the steady-state is reach ed 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 pl asma concentrations but with intraleukocyte concentrations. Drug inter actions studies show that the biological effects of colchicine were no t related to plasma concentrations but with intraleukocyte concentrati ons. Drug interactions may occur when colchicine is associated to drug s which interact with cytochrome P450 and/or P-glycoprotein and modify renal and/or hepatic clearances. The therapeutic drug monitoring of c olchicine during these circumstances could allow tp prevent teh observ ation of side effects.