Plasma kinetics and biliary excretion of colchicine in patients with chronic liver disease after oral administration of a single dose and after long-term treatment.

Plasma kinetics and biliary excretion of colchicine in patients with chronic liver disease were evaluated after oral administration of a single dose and after long-term treatment. A single oral dose of 1 mg colchicine led to a mean peak concentration of 3.60 +/- 1.04 ng/ml at a peak time of 2.16 +/- 0.34 h and a mean area under the plasma concentration time curve, extrapolated from time 0 to infinity, of 24.90 +/- 8.47 ng.h/ml. Comparable values were obtained after repeated administration. Distribution half-life was 2.83 +/- 0.74 h, and terminal plasma half-life was 9.81 +/- 2.08 h; the mean apparent volume of distribution and the mean apparent plasma clearance were 1448 +/- 4061 and 175.3 +/- 47.6 1/h, respectively. Colchicine concentrations in bile (2025 +/- 1368 ng/ml) were clearly higher than in plasma. Long-term treatment with colchicine (1 mg/day) in patients with various stages of primary biliary cirrhosis (PBC) was associated with colchicine concentrations varying from < 0.15 to 2.0 ng/ml, with a slight tendency to higher concentrations in PBC stages III-IV than I-II. Although about 20% of colchicine is excreted in bile within 24 h, accumulation of colchicine may appear only in patients with advanced liver disease and cholestasis.