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
| Molecular Formula | C22H25NO6 |
| Molecular Weight | 399.437 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
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 |
|||
| 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 |
|
| Colchicine myopathy in a case of familial Mediterranean fever: immunohistochemical and ultrastructural study of accumulated tubulin-immunoreactive material. | 1992 |
|
| Serum interleukin-2 and tumor necrosis factor-alpha in primary biliary cirrhosis: decrease by colchicine and relationship to HLA-DR4. | 1992 Apr |
|
| Colchicine-induced myoneuropathy in a renal transplant patient. | 1992 Jun |
|
| [Treatment of AL-amyloidosis and some other types of amyloidosis]. | 2001 Jan |
|
| Abstracts of the Fourth International Symposium on Molecular Insect Science. May 28-June 2, 2002. Tucson, Arizona, USA. | 2002 |
|
| [Neurotoxic effects of medications: an update]. | 2004 |
|
| 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 |
|
| Colchicine myotoxicity: case reports and literature review. | 2004 Dec |
|
| Cytoskeletal myotoxicity from simvastatin and colchicine. | 2004 Dec |
|
| Analysis of ATP-binding cassette transporter expression in drug-selected cell lines by a microarray dedicated to multidrug resistance. | 2004 Dec |
|
| RLIP76 (RALBP1)-mediated transport of leukotriene C4 (LTC4) in cancer cells: implications in drug resistance. | 2004 Dec 20 |
|
| [Abdominal pain and recurrent cholestatic jaundice]. | 2004 Jun 9 |
|
| Acute poisoning with autumn crocus (Colchicum autumnale L.). | 2004 Mar 31 |
|
| Myelodysplasia and acute myeloid leukaemia in a case of rheumatoid arthritis with secondary amyloidosis treated with chlorambucil. | 2004 May |
|
| Establishment of a P-glycoprotein substrate screening model and its preliminary application. | 2004 May 1 |
|
| [Experimental study on Sorbaria sorbifolia extract against chronic liver damage in rats]. | 2004 Oct |
|
| Celastraceae sesquiterpenes as a new class of modulators that bind specifically to human P-glycoprotein and reverse cellular multidrug resistance. | 2004 Oct 1 |
|
| Effects of colchicine on the maximum biliary excretion of cholephilic compounds in rats. | 2004 Sep |
|
| RhoA/ROCK and Cdc42 regulate cell-cell contact and N-cadherin protein level during neurodetermination of P19 embryonal stem cells. | 2004 Sep 5 |
|
| Implication of cyclin-dependent kinase 5 in the neuroprotective properties of lithium. | 2005 |
|
| Monozygotic twins concordant for intestinal Behçet's disease. | 2005 Apr |
|
| [Acute coronary syndrome after diclofenac induced coronary spasm]. | 2005 Apr |
|
| Establishment and characterization of new cellular lymphoma model expressing transgenic human MDR1. | 2005 Apr |
|
| Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study. | 2005 Aug 1 |
|
| Induction of resistance to Aplidin in a human ovarian cancer cell line related to MDR expression. | 2005 Dec |
|
| Acute myopathy in a patient with concomitant use of pravastatin and colchicine. | 2005 Jul-Aug |
|
| Chromosomal aberrations in lymphocytes of healthy subjects and risk of cancer. | 2005 May |
|
| Acute renal failure associated with an accidental overdose of colchicine. | 2005 Oct |
|
| [Nephrogenic diabetes insipidus induced by colchicine--a case report]. | 2005 Sep |
|
| [A case report of acute neuromyopathy induced by concomitant use of colchicine and bezafibrate]. | 2005 Sep |
|
| Tetraparesis associated with colchicine is probably due to inhibition by verapamil of the P-glycoprotein efflux pump in the blood-brain barrier. | 2005 Sep 17 |
|
| An unusual cause of renal amyloidosis secondary to gout: the first description of familial occurrence. | 2006 |
|
| Expression of corticosterone-binding globulin in the rat hypothalamus. | 2006 Apr |
|
| Colchicine myoneuropathy in chronic renal failure patients with gout. | 2006 Apr |
|
| Involvement of cytoskeleton in AhR-dependent CYP1A1 expression. | 2006 Apr |
|
| 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 |
|
| Colchicine and HMG Co-A reductase inhibitors induced myopathy-a case report. | 2006 Dec |
|
| Comparison of the mutagenic potential of 17 physical and chemical agents analyzed by the flow cytometry mutation assay. | 2006 Dec 1 |
|
| Colchicine therapy and the cognitive status of elderly patients with familial Mediterranean fever. | 2006 Jul |
|
| Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression. | 2006 Jul 26 |
|
| [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 |
|
| Sweet's syndrome from an Indian perspective: a report of four cases and review of the literature. | 2006 Jun |
|
| A role for mixed lineage kinases in granule cell apoptosis induced by cytoskeletal disruption. | 2006 Mar |
|
| Synthesis and biological evaluation of B-ring modified colchicine and isocolchicine analogs. | 2006 May 15 |
|
| 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.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 19:32:51 GMT 2023
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admin
on
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| Record UNII |
7JX9WZ3SJ5
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| Record Status |
Validated (UNII)
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| Record Version |
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7JX9WZ3SJ5
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