Pharmacokinetics of colchicine: a review of experimental and clinical data.

Thanks to the development of a sensitive and specific radioimmunoassay for colchicine, the pharmacokinetics of colchicine is now well-established after single oral doses. Absorption is characterized by a zero-order rate constant while disposition appears biexponential with a rapid distribution phase (t1/2 = 1.8 h) and a long elimination phase (t1/2 = 20 h). All studies confirm the large total body clearance (35 l/h) predominantly by the extrarenal route and the large distribution volume (700 l). Further studies need to be performed to investigate colchicine absorption and to describe the metabolic pathway of the drug. To date, relationships between colchicine plasma levels and pharmacological effects have not been defined. Monitoring of plasma levels in patients with familial Mediterranean fever should improve treatment with colchicine. However, the therapeutic range has not been precisely determined. The use of colchicine in the treatment of liver cirrhosis and primary biliary cirrhosis is a recent development; so, assuming that a large part of total body clearance depends on hepatic function, the influence of hepatic diseases on colchicine disposition needs to be investigated in order to define the most appropriate therapeutic dosing.