化合物信息

Drug Groups

approved

Description

A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [PubChem]

Indication

For treatment and relief of pain in attacks of acute gouty arthritis.

Pharmacology

Colchicine is a highly poisonous alkaloid, originally extracted from plants of the genus Colchicum (Autumn crocus, also known as the "Meadow saffron"). Originally used to treat rheumatic complaints and especially gout, it was also prescribed for its cathartic and emetic effects. Its present medicinal use is mainly in the treatment of gout; as well, it is being investigated for its potential use as an anti-cancer drug. It can also be used as initial treatment for pericarditis and preventing recurrences of the condition.

Toxicity

The onset of toxic effects is usually delayed for several hours or more after the ingestion of an acute overdose. Nausea, vomiting, abdominal pain, and diarrhea occur first. The diarrhea may be bloody due to hemorrhagic gastroenteritis. Burning sensations of the throat, stomach, and skin may be prominent symptoms. Extensive vascular damage may result in shock. Kidney damage, evidenced by hematuria and oliguria, may occur. Muscular weakness may be marked, and ascending paralysis of the central nervous system may develop; the patient usually remains conscious. Delirium and convulsions may occur. Death due to respiratory arrest may result. Although death from the ingestion of as little as 7 mg has been reported, much larger doses have been survived .

Affected Organisms

Biotransformation

Probably hepatic. Although colchicine metabolites have not been identified in humans, metabolism by mammalian hepatic microsomes has been demonstrated in vitro.

Absorption

Colchicine is rapidly absorbed after oral administration, probably from the jejunum and ileum. However, the rate and extent of absorption are variable, depending on the tablet dissolution rate; variability in gastric emptying, intestinal motility, and pH at the absorption site; and the extent to which colchicine is bound to microtubules in gastrointestinal mucosal cells.

Half Life

Elimination half-life is approximately 1 hour in healthy subjects, although a study with an extended sampling time reported mean terminal elimination half-life values of approximately 9 to 10.5 hours. Other studies have reported half-life values of approximately 2 hours in patients with alcoholic cirrhosis and approximately 2.5 hours in patients with familial Mediterranean fever.

Protein Binding

Low to moderate (30 to 50%).

Elimination

In healthy volunteers (n=12) 40 – 65% of 1 mg orally administered colchicine was recovered unchanged in urine.
Enterohepatic recirculation and biliary excretion are also postulated to play a role in colchicine elimination.

Distribution

* 5 to 8 L/kg [healthy young volunteers]

Clearance

* 0.17 L/hr/kg [familial Mediterranean fever patients with end-stage renal disease]
* 0.73 L/hr/kg [familial Mediterranean fever patients with normal renal function]

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