Biliary excretion of colchicine.

After intravenous administration of 3H-colchicine (0.2 mg/kg) to rats, 68 percent was excreted in the feces in 48 hours suggesting bile might be the major route of excretion for colchicine. Rats with cannulated bile ducts excreted 50 percent of a 2 mg/kg dose into the bile within 2 hours; half of this was colchicine, and the rest was desmethylcolchicine and more polar metabolites. Colchicine was excreted into the bile of the rat against a bile/plasma concentration gradient of 800 which resulted from a liver/plasma ratio of 15 and a bile/liver ratio of 60. The biliary excretion of colchicine varied widely among the hamster, dog and rabbit. Of the administered colchicine, 32, 20 and 16 percent were excreted by the hamster, dog and rabbit, respectively, within 2 hours. There was also a species difference in the percentage of the radioactivity present in bile as the parent drug. In the hamster, dog and rabbit, the percentage of radioactivity excreted into the bile as colchicine was 45, 34 and 72 percent, respectively. These species excreted colchicine into the bile against a bile/plasma gradient ranging from 19 to 870. Partition of these gradients between liver/plasma and bile/liver ratios demonstrated that both ratios were greater than one, suggesting that colchicine is excreted by an active process. The liver/bile gradient was always the larger of the two ratios.