Colchicine (Colchicina; Condylon; Colsaloid; Colchicinum) is a mitotic/tubulin inhibitor that inhibits microtubule polymerization (also called microtubule disrupting agent or tubulin inhibitor) with potential anticancer and anti-inflammatory effects. Its IC50 is less than 10 nM, which means it inhibits the growth of cancer cells. A medication called colchicine, which is approved to treat gout, is also being studied for possible anticancer properties. Microtubule destabilizers, such as colchicine, encourage the depolymerization of microtubules. Colchicum autumnale L., a poisonous meadow saffron, yielded colchicine, the first tubulin destabilizing compound. Colchicine was authorized in 2009 for the management of familial Mediterranean fever and gout. Strong antimitotic and anticancer properties were also shown by colchicine. Colchicine's severe side effects, which include anemia, gastrointestinal distress, bone marrow damage, and neutropenia, prevented it from being developed clinically as an anticancer treatment.

Physicochemical Properties

Molecular Formula	C22H25NO6
Molecular Weight	399.44
Exact Mass	399.168
Elemental Analysis	C, 66.15; H, 6.31; N, 3.51; O, 24.03
CAS #	64-86-8
Related CAS #	Colchicine-d6;1217651-73-4;Colchicine-d3;1217625-62-1
PubChem CID	6167
Appearance	White to light yellow solid powder
Density	1.3±0.1 g/cm3
Boiling Point	726.0±60.0 °C at 760 mmHg
Melting Point	150-160 °C (dec.)(lit.)
Flash Point	392.9±32.9 °C
Vapour Pressure	0.0±2.4 mmHg at 25°C
Index of Refraction	1.585
LogP	0.92
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	29
Complexity	740
Defined Atom Stereocenter Count	1
SMILES	O(C([H])([H])[H])C1C(=C(C([H])=C2C=1C1=C([H])C([H])=C(C(C([H])=C1[C@]([H])(C([H])([H])C2([H])[H])N([H])C(C([H])([H])[H])=O)=O)OC([H])([H])[H])OC([H])([H])[H])OC([H])([H])[H]
InChi Key	IAKHMKGGTNLKSZ-INIZCTEOSA-N
InChi Code	InChI=1S/C22H25NO6/c1-12(24)23-16-8-6-13-10-19(27-3)21(28-4)22(29-5)20(13)14-7-9-18(26-2)17(25)11-15(14)16/h7,9-11,16H,6,8H2,1-5H3,(H,23,24)/t16-/m0/s1
Chemical Name	N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
Synonyms	Colchicina; Condylon; Colsaloid; Colchicine; Colchicinum
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Microtubule/Tubulin
ln Vitro	Experiencing 1μM The microtubule disrupting agent colchicine caused rat cerebellar granule cells (CGC) to undergo apoptosis. A moderate but progressive increase in the resting intracellular Ca2+ concentration is also brought on by colchicine treatment[1], as well as changes in the Ca2+ responses to chemical depolarization. Colchicine binds to the main structural element of microtubules, the soluble tubulin heterodimer, to initiate its biological actions. The mechanism of Colchicine binding to brain tubulin is thoroughly examined, and the capacities of tubulins to bind Colchicine from diverse sources are enumerated. Colchicine's high affinity binding to tubulin is attributed to its colchicinoid structure, which is reviewed in relation to its analogues in the Colchicine series. This relationship also sheds light on the structural characteristics of Colchicine. The association's kinetic and thermodynamic features are discussed and assessed in relation to the binding mechanism. Colchicine's low energy electronic spectra exhibit peculiar changes upon binding to tubulin. The nature of the Colchicine-tubulin complex is discussed in relation to the spectroscopic characteristics of Colchicine bound to tubulin. There are attempts to identify the high affinity Colchicine binding site on tubulin[2]. The lesion index measured 24 hours after indomethacin administration shows that colchicine treatment inhibits small intestinal injury caused by indomethacin by 86% (1 mg/kg) and 94% (3 mg/kg). Colchicine suppresses the expression of mature IL-1β and cleaved caspase-1 proteins, but has no effect on NLRP3 or IL-1β mRNA expression[3].
ln Vivo	Vehicle or Colchicine (1 mg/kg) is put on the tongue half an hour before indomethacin. Within 24 hours of indomethacin administration, mice treated with Colchicine had smaller lesions in their small intestine when stained with Evans blue as compared to mice treated with vehicle. Furthermore, compared to mice treated with a vehicle, Colchicine-treated mice exhibit decreased mucosal inflammation and ulceration as well as a reduction in the size and quantity of lesions. This was revealed by histological examination. When administered at doses of 1 mg/kg and 3 mg/kg (by 86% and 94%, respectively), colchicine treatment dramatically lowers the lesion index in comparison to vehicle treatment. Treatment with colchicine markedly reduces the protein levels of mature IL-1β by 56% and 69%, respectively, at doses of 1 mg/kg and 3 mg/kg, without changing pro-IL-1β levels.
Enzyme Assay	Spending time in 1μM In rat cerebellar granule cells (CGC), the microtubule disrupting agent colchicine caused apoptosis. In addition, administering colchicine results in a gradual but moderate rise in the resting intracellular Ca2+concentration as well as changes in the Ca2+ responses to chemical depolarization [...]. By binding to the soluble tubulin heterodimer, which is the main building block of the microtubule, colchicine has its biological effects. An extensive examination of the mechanism of Colchicine binding to brain tubulin is conducted, along with a summary of the tubulins' capacity to bind Colchicine from all sources. Insight into the structural characteristics of Colchicine that enable its high affinity binding to tubulin is gained from the correlation between the structure of the colchicinoid and tubulin binding activity. This relationship is also examined for Colchicine series analogs. The association's kinetic and thermodynamic features are discussed and assessed in relation to the binding mechanism. Colchicine's low energy electronic spectra exhibit peculiar changes upon binding to tubulin. The nature of the Colchicine-tubulin complex is discussed in relation to the spectroscopic characteristics of Colchicine bound to tubulin. There are attempts to identify the tubulin's high affinity Colchicine binding site[2]. The lesion index 24 hours after indomethacin administration shows that colchicine treatment inhibits 86% (1 mg/kg) and 94% (3 mg/kg) of indomethacin-induced small intestinal injury. Without influencing the mRNA expression of NLRP3 and IL-1β, colchicine suppresses the protein expression of mature IL-1β and cleaved caspase-1.
Cell Assay	HeLa cells are grown in 6-well plates, and after two hours, they are treated with 100 μM EBI. After that, they are treated with KXO1, vinblastine, or colchicine at varying concentrations. After using radioimmuno_x005fprecipitation assay buffer to extract the total protein, β~-tubulin is analyzed using Western blot analysis. The loading control is GAPDH. The process of Western blotting is carried out.
Animal Protocol	Mice: Male 8-week-old mice that are free of specific pathogens are used. Both NLRP3?/? mice and wild-type C57BL/6 mice on a C57BL/6 background are employed. 30 minutes before indomethacin is given, either a vehicle or 1 or 3 mg/kg of Colchicine is given orally to investigate the impact of Colchicine on NSAID-induced small intestinal damage. Three hours after being treated with indomethacin, mice were given intraperitoneal injections of either mouse recombinant IL-1β (0.1 μg/kg) or sterilized phosphate buffered saline. Before indomethacin is given to NLRP3?/? mice, vehicle or colchicine (1 or 3 mg/kg) is also given. 24 hours after indomethacin is administered, the lesion index is assessed, and 6 hours later, the mRNA and protein expression of inflammasome components is investigated.
ADME/Pharmacokinetics	Absorption, Distribution and Excretion Colchicine is rapidly absorbed after oral administration from the gastrointestinal tract. The bioavailability of colchicine is about 45%: one study suggests that colchicine bioavailability is highly variable, ranging from 24 to 88%. In healthy adults, the mean Cmax of 2.5 ng/mL (range 1.1 to 4.4 ng/mL) was achieved in one to two hours (range 0.5 to 3 hours) after a single dose administered under fasting conditions. In a multiple-dose study of colchicine administration at a dose of 1 mg per day, steady-state concentrations were achieved by day 8 following administration. Administration of colchicine with food does not affect the colchicine absorption rate but decreases the extent of colchicine by approximately 15%. In a pharmacokinetic study of healthy research subjects who received 1 mg of oral colchicine, about 40% to 65% of the dose was recovered in the urine in the form of an unchanged drug. Colchicine undergoes enterohepatic recirculation and biliary excretion. The mean apparent volume of distribution in young and healthy patients is about 5-8 L/kg. It is known to cross the placenta and distribute into the breast milk. Colchicine has been found to distribute to various tissues, mainly into the bile, liver, and kidney tissues. Smaller amounts have been detected in the heart, lungs, intestinal tissue, and stomach. In one pharmacokinetic study involving patients who received a single oral dose of 0.6 mg colchicine, the clearance was 0.0321 ± 0.0091 mL/min in young, healthy adults and 0.0292 ± 0.0071 mL/min in adults between the ages of 60 and 70 years. Patients with end-stage renal impairment showed a 75% lower clearance of colchicine. In a pharmacokinetic study of patients with Familial Mediterranean Fever (FMF), the apparent mean clearance was calculated at 0.726 ± 0.110 L/h/kg. 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. For more Absorption, Distribution and Excretion (Complete) data for COLCHICINE (12 total), please visit the HSDB record page. Metabolism / Metabolites Colchicine is metabolized in the liver. It undergoes CYP3A4-mediated demethylation into major metabolites, 2-O-demethylcolchicine and 3-O-demethylcolchicine. It also forms one minor metabolite, 10-O-demethylcolchicine ([colchiceine]). Plasma levels of these metabolites are less than 5% of parent drug. 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. ... Biological Half-Life After several doses of 0.6 mg twice daily, the average elimination half-life of colchicine ranges from 26.6 to 31.2 hours. Another study reported the elimination half-life ranging to be 20 to 40 hours. Following IV administration of a single therapeutic dose (as of August 2008, IV preparations are no longer commercially available in the US), colchicine is rapidly removed from the plasma; plasma half-life is about 20 minutes. The drug has a half-life of about 60 hours in leukocytes. The elimination half life is variable, ranging from 4.4 hours in normal patients to 30 hours or more in elderly patients. A therapeutic dose produced a half life of 18.8 hours in patients with renal dysfunction. After a single 2 mg intravenous dose the average plasma half life is 20 minutes. Plasma half-life is increased in severe renal disease (40 min) and decreased in severe hepatic disease (9 min).
Toxicity/Toxicokinetics	Toxicity Summary IDENTIFICATION: Colchicine is an antigout preparations. Colchicine is available as tablets and, in some countries, as injectable solutions. Colchicine is an alkaloid of Colchicum autumnale (autumn crocus, meadow saffron). Colchicum is also present in Gloriosa superba. Colchicine is a pale yellow odorless powder or scales. It darkens on exposure to light. Colchicine is used for acute gout attacks to reduce pain and inflammation. It may be used on long-term basis to prevent or reduce the frequency of attacks. Colchicine is used on long-term basis to prevent fever and recurrent polyserositis. Colchicine is effective in preventing the amyloidosis in this condition. Colchicine has been showed to be effective in the treatment of articular, cutaneous and mucosal symptoms. Colchicine has been used in the treatment of scleroderma and sarcoidosis. HUMAN EXPOSURE: Main risks and target organs: Colchicine exerts a multiorgan toxicity. The main toxic effects are related to the effects of colchicine on cellular division and account for diarrhea, bone marrow depression, alopecia. Other acute effects are hypovolemia, shock, and coagulation disturbances, which may lead to death. Summary of clinical effects: Toxic manifestations appear after a delay of 2 to 12 hours following ingestion or parenteral administration. Symptomatology progresses in three stages: Stage I (Day 1 to 3) gastrointestinal and circulatory phase: Severe gastrointestinal irritation: Nausea, vomiting, abdominal cramps, severe diarrhea. Dehydration, hypovolemia, shock. Cardiogenic shock may occur and may result in death within the first 72 hours. Hypoventilation, acute respiratory distress syndrome. Stage II (Day 3 to 10) bone marrow aplasia phase: Bone marrow aplasia with agranulocytosis. Coagulation disorders with diffuse hemorrhages. Rhabdomyolysis, polyneuritis, myopathy, acute renal failure and infections. Stage III: (After 10 day) recovery phase: Alopecia. Routes of entry: Oral: Oral absorption is the most frequent cause of intoxication. Parenteral: Intoxications after parenteral administration are rare, however, the toxic dose appears to be lower than the oral toxic dose. A fatal bone marrow aplasia in a 70 year-old man after 10 mg intravenous colchicine over 5 days. Intoxication with multisystemic reactions after instillation of colchicine into the penile urethra for treatment of condyloma acuminata. Absorption by route of exposure: Oral: Rapidly absorbed from the gastro-intestinal tract. Peak plasma concentration is reached 0.5 to 2 hours after ingestion. Half time of absorption is 15 minutes. Absorption may be modified by pH, gastric contents, intestinal motility. Colchicine is not totally absorbed. There is an important hepatic first pass effect. Colchicine distributes in a space larger than that of the body. In severe renal or liver diseases the volume of distribution is smaller. Colchicine accumulates in kidney, liver, spleen, gastro-intestinal wall and leucocytes and is apparently excluded in heart, brain, skeletal muscle. Colchicine crosses the placenta and has also been found in maternal milk. Biological half-life by route of exposure: Parenteral: After a single 2 mg intravenous dose the average plasma half-life is 20 minutes. Plasma half-life is increased in severe renal disease (40 min) and decreased in severe hepatic disease (9 min). Oral: 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. Metabolism: 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. Elimination by route of exposure: Colchicine is excreted unchanged (10 to 20 percent) or as metabolites. Oral: Urinary excretion amount to 16 to 47% of an administered dose. 50 to 70% of colchicine is excreted unchanged and 30 to 50% as metabolites. 20% of the dose administered is excreted in urine in the first 24 hours and 27.5% in the first 48 hours. Colchicine is detected in urine up to 7 to 10 days after ingestion. Urinary excretion is increased in patients with impaired hepatic function. Bile: 10 to 25% of colchicine is excreted in the bile. Feces: Large amounts of the drug are excreted in the feces. Breast Milk: Colchicine may be eliminated in breast milk. Intravenous: Feces: After intravenous administration 10 to 56% is excreted in the feces within the first 48 hours. Breast Milk: Colchicine may be eliminated in breast milk. Mode of action: Colchicine binds to tubulin and this prevents its polymerization into microtubules. The binding is reversible and the half-life of the colchicine-tubulin complex is 36 hours. Colchicine impairs the different cellular functions of the microtubule: separation of chromosome pairs during mitosis (because colchicine arrests mitosis in metaphase), ameboid movements, phagocytosis. Mitosis blockade accounts for diarrhoea, bone marrow depression and alopecia. Colchicine may have a direct toxic effect on muscle, peripheral nervous system and liver. Inhibition of cellular function does not, however, account for all the organ failures seen in severe overdose. Pharmacodynamics: Gout inflammation is initiated by urate crystals within tissues. The crystals are ingested by neutrophils but this leads to the release of enzymes and the destruction of the cells. Chemotactic factors are released and attract more neutrophils. Colchicine may act by preventing phagocytosis, the release of chemotactic factors and the response of neutrophils. Colchicine has other properties such as antipyretic effects, respiratory depression, vasoconstriction and hypertension. Adults: Oral: The severity and the mortality rate of the poisoning is directly related to the dose ingested. Intravenous: A fatal bone marrow aplasia in a 70-year-old patient is reported. The enhanced toxicity of intravenous colchicine is probably due to the higher bioavailability of colchicine after parenteral administration. Teratogenicity: Colchicine is contraindicated in pregnancy as Down's syndrome and spontaneous abortion have been reported. Colchicine should be discontinued three months prior to conception. Interactions: A case of acute cyclosporin nephrotoxicity induced by colchicine administration has been reported. Colchicine may interfere with cyclosporin pharmacokinetics by increasing cyclosporin plasma levels either by enhancing cyclosporin absorption or by reducing its hepatic metabolism. Main adverse effects: Gastrointestinal symptoms are a common complication of chronic colchicine therapy. Fatal outcomes have been reported after intravenous colchicine therapy. Gastrointestinal: vomiting, diarrhoea, abdominal discomfort, paralytic ileus, malabsorption syndrome with steatorrhea. Hematological: Bone marrow depression with agranulocytosis, acute myelomonocytic leukaemia, multiple myeloma, thrombocytopenia. Neurological: Peripheral neuritis, myopathy and rhabdomyolysis. Dermatological: Allergic reactions are rare urticaria; oedema may be seen. Alopecia has been reported after chronic treatment. Reproductive system: A reversible, complete azoospermia has been reported. Metabolic: Colchicine is capable of producing a reversible impairment of vitamin B12 absorption. Porphyria cutanea tarda has been reported. Others: Hyperglycemia has been reported in a 58-year-old woman who ingested colchicine and developed transient diabetes mellitus has been reported. Hyperlipemia: A transient hyperlipemia has been reported. Hyperuricemia: A transient hyperuricemia has also been noted. Hyperthermia-fever: Occurrence of fever may be relate to an infectious complication, especially during the stage of aplasia. Special risks: Pregnancy: Two cases of Down's syndrome babies have been reported. The obstetric histories of 36 women with familial Mediterranean fever on long-term colchicine treatment between 3 and 12 years have been reported. Seven of 28 pregnancies ended in miscarriage. Thirteen women had periods of infertility. All 16 infants born to mothers who had taken colchicine during pregnancy were healthy. The authors do not advise discontinuation of colchicine before planned pregnancy but recommend amniocentesis for karyotyping and reassurance. Breast-feeding: As colchicine is eliminated in the breast milk breast-feeding should be avoided. Interactions Colchicine has been shown to induce reversible malabsorption of vitamin B12, apparently by altering the function of ileal mucosa. Results of animal studies have suggested that colchicine may enhance response to sympathomimetic agents and CNS depressants. (1) Renal failure, either pre-existing or induced by a nephrotoxic drug, increases the risk of adverse effects in patients taking colchicine; (2) Combining colchicines with a macrolide (except for spiramycin) carries a risk of life-threatening pancytopenia; (3) Ciclosporin co-administration can aggravate the neuromuscular adverse effects of colchicine; (4) Combining colchicine with lipid-lowering drugs (statins and fibrates) can cause myopathy; (5) Several mechanisms have been implicated: competition for cytochrome P450 or P-glycoprotein, additive adverse effects (especially on muscle), and colchicine accumulation due to a reduction in its renal excretion; (6) Patients with gout should use colchicine only after failure of symptomatic treatment: ice application, paracetamol, and possibly ibuprofen, a nonsteroidal antiinflammatory drug with well-documented adverse effects; (7) If colchicine is nevertheless used, it should be at the minimum effective dose. Close clinical monitoring is required in order to detect early signs of adverse effects, especially diarrhea, the earliest sign in patients with renal failure and in the elderly. Colchicine and 3-hydroxy-3-methy-glutaryl coenzyme A (HMG-CoA) reductase inhibitors are well known to cause myopathy. Myotoxicity is dose-dependent in both drugs; therefore, the onset of symptoms usually takes months or years. We report the case of a patient with chronic renal failure who had been taking simvastatin for 2 years and developed acute weakness 2 weeks after the start of treatment with colchicines for recurrent gout. The electromyography and elevated muscle enzymes indicated that his symptoms were caused by myopathy. When this patient stopped taking both drugs, his weakness resolved rapidly. Acute myopathy induced by combination therapy with colchicines and simvastatin is rare. In patients with chronic renal failure, co-administration of colchicine with simvastatin may accelerate the onset of myopathy because CYP3A4 (part of cytochrome P450) is crucial in the breakdown of both drugs. When adding colchicine to a medication regimen that includes a HMG-CoA reductase inhibitor for patients with renal insufficiency, drugs that are metabolized outside the CYP3A4 system (e.g., fluvastatin and pravastatin) should be selected instead. For more Interactions (Complete) data for COLCHICINE (13 total), please visit the HSDB record page. Non-Human Toxicity Values LD50 Cat intravenous 0.25 mg/kg LD50 Mouse oral 5886 ug/kg LD50 Mouse ip 2 mg/kg LD50 Mouse iv 4.13 mg/kg For more Non-Human Toxicity Values (Complete) data for COLCHICINE (8 total), please visit the HSDB record page.
References	[1]. Colchicine induces apoptosis in cerebellar granule cells. Exp Cell Res. 1995 May;218(1):189-200. [2]. Interactions of colchicine with tubulin. Pharmacol Ther. 1991;51(3):377-401. [3]. Colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome. Sci Rep. 2016 Sep 2;6:32587. [4]. Inhibition of the Glycine Receptor alpha 3 Function by Colchicine. Front Pharmacol. 2020 Jul 30;11:1143.
Additional Infomation	Therapeutic Uses Gout Suppressants Colchicine also is used in the prophylactic treatment of recurrent gouty arthritis. Colchicine has no effect on plasma concentrations or urinary excretion of uric acid; therefore, concomitant administration of allopurinol or a uricosuric agent (e.g., probenecid, sulfinpyrazone) is necessary to decrease serum urate concentrations. Prophylactic doses of colchicine should be administered before the initiation of allopurinol or uricosuric therapy because sudden changes in serum urate concentrations may precipitate acute gout attacks. After the serum urate concentration has been reduced to the desired level and acute gout attacks have not occurred for 3-6 months (some clinicians suggest 1-12 months), colchicine may be discontinued and the patient may be treated with urate lowering agents alone. Colchicine is frequently used in combination with probenecid to facilitate prophylactic therapy in patients with chronic gouty arthritis. The usefulness of the commercially available fixed-dosage preparation is limited, however, because the colchicine present exceeds the amount required by most patients. /Use Included in US product label/ Colchicine is used to relieve attacks of acute gouty arthritis. Nonsteroidal anti-inflammatory agents (NSAIAs) (e.g., indomethacin, ibuprofen, naproxen, sulindac, piroxicam, ketoprofen) are as effective as, and better tolerated than, usual dosages of colchicine for short-term use in relieving acute attacks of gouty arthritis. Corticosteroids also are used to relieve acute attacks of gouty arthritis. Colchicine is considered a second-line agent; colchicine may be used for the treatment of acute gouty arthritis in patients who have not responded to or who cannot tolerate recommended therapies (i.e., NSAIAs, corticosteroids). /Use Included in US product label/ 96 patients aged 15 yr or more with complete or incomplete Behcet's disease, whose visual acuity was 20/40 or less, and who had experienced at least 2 episodes of ocular attack during the 16 wk before the study were selected. 47 patients received cyclosporin (10 mg/kg) and 49 colchicine (1 mg/kg) daily for 16 wk. The frequency of ocular attack was reduced more in the cyclosporin group than in the colchicine group (p < 0.001). The severity of ocular attacks was also less severe after cyclosporin than after colchicine (p < 0.001). Colchicine alleviated oral aphthous ulcer in 10 patients (20%). Dermal lesions were alleviated in 15% of the colchicine group. Clinical symptoms were improved in 33% for the colchicine group, and 10 cases were aggravated. OKT4/OKT8 ratios were 1.44 in the colchicine group before the study and 1.46 after treatment. Frequently observed side effects of colchicine were hirsutism (2 patients) and renal dysfunction (2 patients). Treatment was stopped because of hepatic dysfunction in 2 colchicine cases. For more Therapeutic Uses (Complete) data for COLCHICINE (11 total), please visit the HSDB record page. Drug Warnings Colchicine injection has been available in the US since the 1950s and has been used for the treatment of acute attacks of gout. Colchicine injection preparations that have been commercially available have not been approved by the US Food and Drug Administration (FDA). Serious adverse events, some fatal, have been reported in patients receiving colchicine injection. Because of the potentially serious health risks associated with unapproved colchicine injection, FDA announced on February 8, 2008, that it would take enforcement action (e.g., seizure, injunction, other judicial proceeding) against all firms, including compounding pharmacies, attempting to manufacture, ship, or deliver colchicine injection. FDA will implement enforcement action against all firms attempting to manufacture or ship colchicine injection products that do not have a National Drug Code (NDC) number on or after February 8, 2008. For colchicine injection products with an NDC number, FDA will take enforcement action against all firms attempting to manufacture such products on or after March 10, 2008, and against firms that ship such products on or after August 6, 2008. Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia with colchicine used in therapeutic doses have been reported. Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses. Patients with renal dysfunction and elderly patients, even those with normal renal and hepatic function, are at increased risk. The most common adverse reaction is diarrhea (23%). Pharyngolaryngeal pain was seen in 3% of patients treated for gout flares. Gastrointestinal tract adverse effects are the most frequent side effects in patients initiating colchicine, usually presenting within 24 hours, and occurring in up to 20% of patients given therapeutic doses. Typical symptoms include cramping, nausea, diarrhea, abdominal pain, and vomiting. These events should be viewed as dose-limiting if severe as they can herald the onset of more significant toxicity. For more Drug Warnings (Complete) data for COLCHICINE (13 total), please visit the HSDB record page. Pharmacodynamics Colchicine ameliorates the symptoms of gout and Familial Mediterranean fever. It possesses anti-inflammatory, anti-fibrotic, and cardiovascular protective effects. Colchicine was shown to exhibit anticancer properties, such as the inhibition of cancer cell migration and angiogenesis. Colchicine has a narrow therapeutic window.

Solubility Data

Solubility (In Vitro)	DMSO: ~80 mg/mL (~200.3 mM) Water: ~80 mg/mL (~200.3 mM) Ethanol: ~80 mg/mL (~200.3 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 2.78 mg/mL (6.96 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5035 mL	12.5175 mL	25.0350 mL
	5 mM	0.5007 mL	2.5035 mL	5.0070 mL
	10 mM	0.2504 mL	1.2518 mL	2.5035 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.