Colchicine

Colchicine is a naturally occuring alkaloid, obtained from plants of the lily family, including Colchicum autumnale, which has been used for medicinal purposes since the time of ancient Greece. Following oral administration, colchicine is rapidly absorbed in the jejunum and ileum, and it undergoes significant hepatic first-pass metabolism. Colchicine is primarily metabolized in the liver, by the cytochrome P450 enzyme CYP3A4, via demethylation before hepatobiliary excretion in the stool. Colchicine is seen at particularly high concentrations in leucocytes and impairs neutrophil function, macrophage activation and mast cell degranulation. Colchicine has a narrow therapeutic window and a significant variation in the dose required to cause morbidity or mortality, and as little as 6–7 mg has caused death. The use of colchicine in pregnancy is controversial as a result of the potential risks and should only be considered if the potential benefits to the mother outweigh the possible risk to the fetus, e.g. familial Mediterranean fever.