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 c hronic liver disease were evaluated after oral administration of a sin gle dose and after long-term treatment. A single oral dose of 1 mg col chicine led to a mean peak concentration of 3.60 +/- 1.04 ng/ml at a p eak time of 2.16 +/- 0.34 h and a mean area under the plasma concentra tion time curve, extrapolated from time 0 to infinity, of 24.90 +/- 8. 47 ng.h/ml. Comparable values were obtained after repeated administrat ion. Distribution half-life was 2.83 +/- 0.74h, and terminal plasma el imination half-life was 9.81 +/- 2.08 h; the mean apparent volume of d istribution and the mean apparent plasma clearance were 1448 +/- 4061 and 175.3 +/- 47.61/h, respectively. Colchicine concentrations in bile (2025 +/- 1368 ng/ml) were clearly higher than in plasma. Long-term t reatment with colchicine (1 mg/day) in patients with various stages of primary biliary cirrhosis (PBC) was associated with colchicine concen trations varying from <0.15 to 2.0 ng/ml, with a slight tendency to hi gher concentrations in PBC stages III-IV than I-II, Although about 20% of colchicine is excreted in bile within 24 h, accumulation of colchi cine may appear only in patients with advanced liver disease and chole stasis.