Colchicine undergoes some hepatic metabolism. Colchicine is partially deacetylated in the liver. Large amounts of colchicine and of its metabolites undergo enterohepatic circulation. This may explain the occurrence of a second plasma peak concentration observed 5 to 6 hours after ingestion.
Three novel conjugation metabolites of colchicine were identified in rat bile facilitated by enhanced on-line liquid chromatography-accurate radioisotope counting. The known 2- and 3-demethylcolchicines (DMCs) underwent O-sulfate conjugation in addition to the previously described O-glucuronidation. 2-DMC was preferably O-glucuronidated, whereas 3-DMC predominantly yielded O-sulfation conjugates, indicating phase II conjugation regiopreferences. Moreover, M1 was identified as a novel glutathione conjugate and a possible biotransformation pathway for its formation was proposed. The known 2-DMC (M6), 3-DMC (M7), 2-DMC glucuronide (M4), and novel 3-DMC sulfate (M3) were confirmed as the major metabolites. ...
Chronic therapy with colchicine is uncommonly associated with serum aminotransferase or alkaline phosphatase elevations and has, indeed, been used off label as therapy of liver diseases, including alcoholic hepatitis and primary biliary cirrhosis. Despite decades of wide spread use, there have been no published cases of idiosyncratic liver disease attributed to colchicine use. Interestingly, liver biopsies done in patients receiving colchicine often show scattered mitotic figures in hepatocytes (ring mitoses) without accompanying liver cell injury.
In high doses, however, colchicine is associated with severe toxicity which can involve the liver. Intentional as well as accidental overdoses of colchicine can be severe and even fatal, usually presenting with vomiting, diarrhea, weakness and metabolic acidosis followed by rhadbomyolysis, shock, sepsis, coma and multiorgan failure. Liver test abnormalities can occur but may be due to rhabdomyosis rather than liver injury. Acute liver failure may arise later, perhaps as a result of shock and multiorgan failure. Colchicine overdose is rarely associated with frank jaundice or with a hepatitis-like presentation. The liver abnormalities are probably secondary to ischemic injury to the liver or sepsis.
Likelihood score: E (unlikely cause of clinically apparent liver injury).
Colchicine can be absorbed into the body by ingestion, inhalation, or eye contact. Colchicine can also be injected through the skin or administered intravenously. It is unknown whether colchicine can be absorbed through intact skin.
来源:The National Institute for Occupational Safety and Health (NIOSH)
毒理性
吸入症状
看到摄入暴露的迹象/症状。
See Signs/Symptoms Ingestion Exposure.
来源:The National Institute for Occupational Safety and Health (NIOSH)
毒理性
皮肤症状
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来源:The National Institute for Occupational Safety and Health (NIOSH)
毒理性
眼睛症状
与液体秋水仙碱接触可能会产生角膜混浊，这种情况在几周内会自行消散。
Eye contact with liquid colchicine may produce clouding of the cornea that clears in a few weeks.
来源:The National Institute for Occupational Safety and Health (NIOSH)
The absorption of colchicine is rapid but variable. Peak plasma concentrations occur 0.5 to 2 hours after dosing. In plasma, 50% of colchicine is protein-bound. There is significant enterohepatic circulation. The exact metabolism of colchicine is unknown but seems to involve deacetylation by the liver. Only 10% to 20% is excreted in the urine, although this increases in patients with liver disease. The kidney, liver, and spleen also contain high concentrations of colchicine, but it apparently is largely excluded from heart, skeletal muscle, and brain. The plasma half-life of colchicine is approximately 9 hours, but it can be detected in leukocytes and in the urine for at least 9 days after a single intravenous dose.
... Two cases involving suicide by the ingestion of medications marketed in France /is reported/. In case 1, only heart blood was taken after body external examination. In case 2 an autopsy was performed and heart blood, urine, gastric contents and bile were taken for toxicological analysis. Colchicine was assayed in biological specimens by an HPLC-DAD method, after extraction by dichloromethane at pH 8, adding prazepam as internal standard (IS). Analyses were performed on a Symetry C-8 column. Mobile phase was a gradient of acetonitrile/pH 3.8 phosphate buffer. Colchicine is eluted at 13.1 min and the method is linear for blood, urine and bile over the range 4-1000 ng/mL. LOQ is 4 ng/mL. The concentrations of colchicine detected are: case 1: heart blood 13 ng/mL; case 2: heart blood 66 ng/mL, urine 500 ng/mL, gastric content 12 ng/mL, bile 5632 ng/mL. Our findings are in the range of lethal concentrations previously described, but there is no correlation with the amount of ingested drug. Even after massive overdose, it could be impossible to detect colchicine in blood, and as there is a widespread enterohepatic recirculation before excretion in bile and feces, bile is the target sample to analyse. We conclude in both cases that the cause of death was suicide with colchicine. It appears very important to perform an autopsy in order to obtain bile, urine, heart blood and femoral blood.
After oral administration plasma concentrations reach a peak within 0.5 to 2 hours and afterwards decrease rapidly within 2 hours. The plasma half-life is 60 minutes. Colchicine may remain in tissues for as long as 10 days.
Information was available on urinary excretion in 5 cases. Concentrations in urine are 10 to 80 fold higher than those in plasma. Four to 25 per cent of the dose ingested was excreted in urine over three to ten days. Excretion was specially high during the first 24 hours following ingestion. Colchicine is eliminated in urine up to the tenth day.
