La colchicine: données récentes sur sa pharmacocinétique et sa pharmacologie clinique

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