Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C22H25NO6 |
| Molecular Weight | 399.437 |
| Optical Activity | UNSPECIFIED |
| Additional Stereochemistry | Yes |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
| Stereo Comments | P-helix |
SHOW SMILES / InChI
SMILES
COC1=CC2=C(C(OC)=C1OC)C3=CC=C(OC)C(=O)C=C3[C@H](CC2)NC(C)=O
InChI
InChIKey=IAKHMKGGTNLKSZ-INIZCTEOSA-N
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
Colchicine is an alkaloid obtained from the plant colchicum autumnale (also known as "meadow saffron"). Colchicine is an alternative medication for those unable to tolerate NSAIDs in gout. Mechanism of action of colchicine is inhibition of microtubule polymerization by binding to tubulin. Availability of tubulin is essential to mitosis, so colchicine effectively unctions as a "mitotic poison" or spindle poison.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2095182 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Preventing | COLCRYS Approved UseColchicine capsules are indicated for prophylaxis of gout flares in adults. Colchicine disrupts the polymerization of β-tubulin into microtubules, thereby preventing the activation, degranulation, and migration of neutrophils to sites of inflammation. Launch Date2009 |
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| Primary | COLCRYS Approved UseColchicine is indicated for Familial Mediterranean fever (FMF) in adults and children 4 years or older Launch Date2009 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.68 ng/mL |
0.6 mg single, oral dose: 0.6 mg route of administration: Oral experiment type: SINGLE co-administered: |
COLCHICINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
2.16 ng/mL |
0.6 mg single, oral dose: 0.6 mg route of administration: Oral experiment type: SINGLE co-administered: |
COLCHICINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
|
2023.29 pg/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00960323 |
0.6 mg single, oral dose: 0.6 mg route of administration: oral experiment type: single co-administered: |
COLCHICINE plasma | Homo sapiens |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
18.47 ng × h/mL |
0.6 mg single, oral dose: 0.6 mg route of administration: Oral experiment type: SINGLE co-administered: |
COLCHICINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
19.9 ng × h/mL |
0.6 mg single, oral dose: 0.6 mg route of administration: Oral experiment type: SINGLE co-administered: |
COLCHICINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
|
8717.33 pg*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00960323 |
0.6 mg single, oral dose: 0.6 mg route of administration: oral experiment type: single co-administered: |
COLCHICINE plasma | Homo sapiens |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
30.54 h |
0.6 mg single, oral dose: 0.6 mg route of administration: Oral experiment type: SINGLE co-administered: |
COLCHICINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
31.04 h |
0.6 mg single, oral dose: 0.6 mg route of administration: Oral experiment type: SINGLE co-administered: |
COLCHICINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
61% |
COLCHICINE serum | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
50 mg single, oral Overdose |
unknown, 42 years n = 1 Health Status: unknown Age Group: 42 years Sex: M Population Size: 1 Sources: |
Other AEs: Myelosuppression... |
3 mg 1 times / day multiple, oral MTD Dose: 3 mg, 1 times / day Route: oral Route: multiple Dose: 3 mg, 1 times / day Sources: |
unhealthy, 44 years (range: 39.5–48.5 years) n = 15 Health Status: unhealthy Condition: familial Mediterranean fever Age Group: 44 years (range: 39.5–48.5 years) Sex: M+F Population Size: 15 Sources: |
|
1 mg 1 times / week multiple, intravenous Dose: 1 mg, 1 times / week Route: intravenous Route: multiple Dose: 1 mg, 1 times / week Sources: |
unhealthy, 44 years (range: 39.5–48.5 years) n = 15 Health Status: unhealthy Condition: familial Mediterranean fever Age Group: 44 years (range: 39.5–48.5 years) Sex: M+F Population Size: 15 Sources: |
Other AEs: Nausea, Vomiting... Other AEs: Nausea (27%) Sources: Vomiting (13%) Diarrhea (20%) Injection site reactions (20%) Myalgia (27%) Arthralgia (7%) Allergic reaction (7%) |
12 mg single, oral Overdose |
unknown, 56 years n = 1 Health Status: unknown Age Group: 56 years Sex: M Population Size: 1 Sources: |
Other AEs: Rhabdomyolysis... |
1 mg 1 times / day multiple, oral Recommended Dose: 1 mg, 1 times / day Route: oral Route: multiple Dose: 1 mg, 1 times / day Sources: |
unhealthy, 79 years n = 1 Health Status: unhealthy Age Group: 79 years Sex: M Population Size: 1 Sources: |
Disc. AE: Acute pancreatitis, Epigastric pain... AEs leading to discontinuation/dose reduction: Acute pancreatitis (1 patient) Sources: Epigastric pain (severe, 1 patient) Nausea (1 patient) Vomiting (1 patient) |
0.6 mg 2 times / day multiple, oral Dose: 0.6 mg, 2 times / day Route: oral Route: multiple Dose: 0.6 mg, 2 times / day Sources: |
unhealthy n = 49 Health Status: unhealthy Condition: Thoracic Surgery Population Size: 49 Sources: |
Other AEs: Acute respiratory distress syndrome, Fall... Other AEs: Acute respiratory distress syndrome (serious, 3 patients) Sources: Fall (serious, 2 patients) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Myelosuppression | grade 4, 1 patient | 50 mg single, oral Overdose |
unknown, 42 years n = 1 Health Status: unknown Age Group: 42 years Sex: M Population Size: 1 Sources: |
| Vomiting | 13% | 1 mg 1 times / week multiple, intravenous Dose: 1 mg, 1 times / week Route: intravenous Route: multiple Dose: 1 mg, 1 times / week Sources: |
unhealthy, 44 years (range: 39.5–48.5 years) n = 15 Health Status: unhealthy Condition: familial Mediterranean fever Age Group: 44 years (range: 39.5–48.5 years) Sex: M+F Population Size: 15 Sources: |
| Diarrhea | 20% | 1 mg 1 times / week multiple, intravenous Dose: 1 mg, 1 times / week Route: intravenous Route: multiple Dose: 1 mg, 1 times / week Sources: |
unhealthy, 44 years (range: 39.5–48.5 years) n = 15 Health Status: unhealthy Condition: familial Mediterranean fever Age Group: 44 years (range: 39.5–48.5 years) Sex: M+F Population Size: 15 Sources: |
| Injection site reactions | 20% | 1 mg 1 times / week multiple, intravenous Dose: 1 mg, 1 times / week Route: intravenous Route: multiple Dose: 1 mg, 1 times / week Sources: |
unhealthy, 44 years (range: 39.5–48.5 years) n = 15 Health Status: unhealthy Condition: familial Mediterranean fever Age Group: 44 years (range: 39.5–48.5 years) Sex: M+F Population Size: 15 Sources: |
| Myalgia | 27% | 1 mg 1 times / week multiple, intravenous Dose: 1 mg, 1 times / week Route: intravenous Route: multiple Dose: 1 mg, 1 times / week Sources: |
unhealthy, 44 years (range: 39.5–48.5 years) n = 15 Health Status: unhealthy Condition: familial Mediterranean fever Age Group: 44 years (range: 39.5–48.5 years) Sex: M+F Population Size: 15 Sources: |
| Nausea | 27% | 1 mg 1 times / week multiple, intravenous Dose: 1 mg, 1 times / week Route: intravenous Route: multiple Dose: 1 mg, 1 times / week Sources: |
unhealthy, 44 years (range: 39.5–48.5 years) n = 15 Health Status: unhealthy Condition: familial Mediterranean fever Age Group: 44 years (range: 39.5–48.5 years) Sex: M+F Population Size: 15 Sources: |
| Allergic reaction | 7% | 1 mg 1 times / week multiple, intravenous Dose: 1 mg, 1 times / week Route: intravenous Route: multiple Dose: 1 mg, 1 times / week Sources: |
unhealthy, 44 years (range: 39.5–48.5 years) n = 15 Health Status: unhealthy Condition: familial Mediterranean fever Age Group: 44 years (range: 39.5–48.5 years) Sex: M+F Population Size: 15 Sources: |
| Arthralgia | 7% | 1 mg 1 times / week multiple, intravenous Dose: 1 mg, 1 times / week Route: intravenous Route: multiple Dose: 1 mg, 1 times / week Sources: |
unhealthy, 44 years (range: 39.5–48.5 years) n = 15 Health Status: unhealthy Condition: familial Mediterranean fever Age Group: 44 years (range: 39.5–48.5 years) Sex: M+F Population Size: 15 Sources: |
| Rhabdomyolysis | grade 5, 1 patient | 12 mg single, oral Overdose |
unknown, 56 years n = 1 Health Status: unknown Age Group: 56 years Sex: M Population Size: 1 Sources: |
| Acute pancreatitis | 1 patient Disc. AE |
1 mg 1 times / day multiple, oral Recommended Dose: 1 mg, 1 times / day Route: oral Route: multiple Dose: 1 mg, 1 times / day Sources: |
unhealthy, 79 years n = 1 Health Status: unhealthy Age Group: 79 years Sex: M Population Size: 1 Sources: |
| Nausea | 1 patient Disc. AE |
1 mg 1 times / day multiple, oral Recommended Dose: 1 mg, 1 times / day Route: oral Route: multiple Dose: 1 mg, 1 times / day Sources: |
unhealthy, 79 years n = 1 Health Status: unhealthy Age Group: 79 years Sex: M Population Size: 1 Sources: |
| Vomiting | 1 patient Disc. AE |
1 mg 1 times / day multiple, oral Recommended Dose: 1 mg, 1 times / day Route: oral Route: multiple Dose: 1 mg, 1 times / day Sources: |
unhealthy, 79 years n = 1 Health Status: unhealthy Age Group: 79 years Sex: M Population Size: 1 Sources: |
| Epigastric pain | severe, 1 patient Disc. AE |
1 mg 1 times / day multiple, oral Recommended Dose: 1 mg, 1 times / day Route: oral Route: multiple Dose: 1 mg, 1 times / day Sources: |
unhealthy, 79 years n = 1 Health Status: unhealthy Age Group: 79 years Sex: M Population Size: 1 Sources: |
| Fall | serious, 2 patients | 0.6 mg 2 times / day multiple, oral Dose: 0.6 mg, 2 times / day Route: oral Route: multiple Dose: 0.6 mg, 2 times / day Sources: |
unhealthy n = 49 Health Status: unhealthy Condition: Thoracic Surgery Population Size: 49 Sources: |
| Acute respiratory distress syndrome | serious, 3 patients | 0.6 mg 2 times / day multiple, oral Dose: 0.6 mg, 2 times / day Route: oral Route: multiple Dose: 0.6 mg, 2 times / day Sources: |
unhealthy n = 49 Health Status: unhealthy Condition: Thoracic Surgery Population Size: 49 Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| yes | likely (co-administration study) Comment: Although there are no published case reports for colchicine toxicity when co-administered with the 4 inhibitors that the sponsor employed, i.e., voriconazole, fluconazole, cimetidine and propafenone, several published case reports indicate that colchicine toxicity is observed when it is co-administered with drugs that are potent inhibitors of both P-gp and CYP3A4 (e.g., clarithromycin, ketoconazole) as well as potent P-gp inhibitors (e.g., cyclosporine). Page: 2.0 |
|||
| yes | yes (co-administration study) Comment: Co-administration with posaconazole (considered a strong CYP3A4 inhibitor) increased AUC of colchcine by approximately 3-fold; Although there are no published case reports for colchicine toxicity when co-administered with the 4 inhibitors that the sponsor employed, i.e., voriconazole, fluconazole, cimetidine and propafenone, several published case reports indicate that colchicine toxicity is observed when it is co-administered with drugs that are potent inhibitors of both P-gp and CYP3A4 (e.g., clarithromycin, ketoconazole) and strong to moderate inhibitors of CYP3A4 (e.g., grapefruit juice, erythromycin). Page: 2.0 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Colchicine-induced lesions in the rat duodenum. | 1975 |
|
| Evaluation of natural products as inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. | 1991 Jan-Feb |
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| Colchicine myopathy in a case of familial Mediterranean fever: immunohistochemical and ultrastructural study of accumulated tubulin-immunoreactive material. | 1992 |
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| Serum interleukin-2 and tumor necrosis factor-alpha in primary biliary cirrhosis: decrease by colchicine and relationship to HLA-DR4. | 1992 Apr |
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| Acute myopathy induced by colchicine in a cyclosporine treated heart transplant recipient: possible role of the multidrug resistance transporter. | 1999 Aug |
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| Induced differentiation in HT29, a human colon adenocarcinoma cell line. | 1999 Aug |
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| Hypernatraemia and polyuria due to high-dose colchicine in a suicidal patient. | 1999 Jun |
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| Improvement of renal function in patients with chronic gout after proper control of hyperuricemia and gouty bouts. | 2000 Nov |
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| Accumulation of microtubule-based motor protein in a patient with colchicine myopathy. | 2000 Nov 14 |
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| Anti-inflammatory fibrosis suppression in threatened trabeculectomy bleb failure produces good long term control of intraocular pressure without risk of sight threatening complications. | 2002 Dec |
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| Colchicine myopathy: a vacuolar myopathy with selective type I muscle fiber involvement. An immunohistochemical and electron microscopic study of two cases. | 2002 Feb |
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| Colchicine myoneuropathy in a renal transplant patient. | 2002 Jul |
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| 2-Alkoxycarbonylaminopyridines: inhibitors of Mycobacterium tuberculosis FtsZ. | 2002 Jul |
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| Colchicine neuromyopathy: a report of six cases. | 2002 Jul-Aug |
|
| Improvement of combination chemotherapy tolerance by introduction of polycistronic retroviral vector drug resistance genes MGMT and MDR1 into human umbilical cord blood CD34+ cells. | 2002 Mar |
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| Nocodazole-induced p53-dependent c-Jun N-terminal kinase activation reduces apoptosis in human colon carcinoma HCT116 cells. | 2002 Nov 15 |
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| Colchicine-induced acute myopathy in a patient with concomitant use of simvastatin. | 2002 Sep-Oct |
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| Mechanisms by which cAMP increases bile acid secretion in rat liver and canalicular membrane vesicles. | 2003 Aug |
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| Colchicine-induced myopathy in a teenager with familial Mediterranean fever. | 2003 Dec |
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| Permanent activation of the human P-glycoprotein by covalent modification of a residue in the drug-binding site. | 2003 Jun 6 |
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| The role of the cytoskeleton in mechanotransduction in human osteoblast-like cells. | 2003 May |
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| Exocytotic "constipation" is a mechanism of tubulin/lysosomal interaction in colchicine myopathy. | 2003 May 1 |
|
| Case report. Hepatic portal venous gas: transient radiographic finding associated with colchicine toxicity. | 2003 Nov |
|
| Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-2003. A 37-year-old man with a history of alcohol and drug abuse and sudden onset of leg weakness. | 2003 Oct 23 |
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| Colchicine-induced myopathy with myotonia in a patient with chronic renal failure. | 2003 Sep |
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| Microtubule disarray in primary cultures of human hepatocytes inhibits transcriptional activity of the glucocorticoid receptor via activation of c-jun N-terminal kinase. | 2004 Dec |
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| Colchicine myotoxicity: case reports and literature review. | 2004 Dec |
|
| RLIP76 (RALBP1)-mediated transport of leukotriene C4 (LTC4) in cancer cells: implications in drug resistance. | 2004 Dec 20 |
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| [Abdominal pain and recurrent cholestatic jaundice]. | 2004 Jun 9 |
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| Celastraceae sesquiterpenes as a new class of modulators that bind specifically to human P-glycoprotein and reverse cellular multidrug resistance. | 2004 Oct 1 |
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| Effects of colchicine on the maximum biliary excretion of cholephilic compounds in rats. | 2004 Sep |
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| RhoA/ROCK and Cdc42 regulate cell-cell contact and N-cadherin protein level during neurodetermination of P19 embryonal stem cells. | 2004 Sep 5 |
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| [Acute coronary syndrome after diclofenac induced coronary spasm]. | 2005 Apr |
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| Establishment and characterization of new cellular lymphoma model expressing transgenic human MDR1. | 2005 Apr |
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| [Nephrogenic diabetes insipidus induced by colchicine--a case report]. | 2005 Sep |
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| An unusual cause of renal amyloidosis secondary to gout: the first description of familial occurrence. | 2006 |
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| Preplaced cell division: a critical mechanism of autoprotection against S-1,2-dichlorovinyl-L-cysteine-induced acute renal failure and death in mice. | 2006 Aug |
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| Colchicine and HMG Co-A reductase inhibitors induced myopathy-a case report. | 2006 Dec |
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| Comparison of the mutagenic potential of 17 physical and chemical agents analyzed by the flow cytometry mutation assay. | 2006 Dec 1 |
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| Colchicine therapy and the cognitive status of elderly patients with familial Mediterranean fever. | 2006 Jul |
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| Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression. | 2006 Jul 26 |
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| [Effect of the ethyl acetate extract of zhi ju zi on serum makers and the expression of TGF-beta1 in rats with hepatic fibrosis]. | 2006 Jun |
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| Sweet's syndrome from an Indian perspective: a report of four cases and review of the literature. | 2006 Jun |
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| A role for mixed lineage kinases in granule cell apoptosis induced by cytoskeletal disruption. | 2006 Mar |
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| Cyclosporine not the only agent to cause Guillain-Barré-like syndrome after solid-organ transplant. | 2006 Nov |
|
| Microtubules are required for NF-kappaB nuclear translocation in neuroblastoma IMR-32 cells: modulation by zinc. | 2006 Oct |
|
| Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats. | 2007 |
|
| Zinc and the cytoskeleton in the neuronal modulation of transcription factor NFAT. | 2007 Jan |
Sample Use Guides
For prophylaxis of gout flares, the recommended dosage of Colchicine capsules is 0.6 mg once or twice daily. The maximum dose is 1.2 mg per day. Colchicine capsules are administered orally, without regard to meals.
Route of Administration:
Oral
Inhibition of the polymerization of brain tubulin was evaluated. Solution of compound in DMSO in serial dilutions was prepared. Reaction mixture contained 0.25 mg of tubulin, 1.0 M monosodium glutamate and approptiate drug concentrations. The reaction mixtures were incubated at 37 °C for 15 min to allow slow binding drugs like colchicine to bind to the tubulin. The reaction mixtures were then chilled on ice, and the polymerization reaction was followed turbidimetrically for 20 min. Polymer formation was confirmed by evaluation of depolymerization at 0°C. Extent of inhibition of polymerization at 20 min in drug-treated samples was always calculated by comparing them to a pair of drug-free samples in each experimental set.
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SUBSTANCE RECORD
