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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H25NO6.C7H6O3
Molecular Weight 537.5577
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of COLCHICINE SALICYLATE

SMILES

OC(=O)C1=C(O)C=CC=C1.COC2=C(OC)C(OC)=C3C(CC[C@H](NC(C)=O)C4=CC(=O)C(OC)=CC=C34)=C2

InChI

InChIKey=FJDBYGKCGURUGE-NTISSMGPSA-N
InChI=1S/C22H25NO6.C7H6O3/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;8-6-4-2-1-3-5(6)7(9)10/h7,9-11,16H,6,8H2,1-5H3,(H,23,24);1-4,8H,(H,9,10)/t16-;/m0./s1

HIDE SMILES / InChI

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

Molecular Formula C7H6O3
Molecular Weight 138.1207
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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.

CNS Activity

Curator's Comment: Known to be CNS non-penetrant in rats. Human data not available.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
COLCRYS

Approved Use

Colchicine 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 Date

1.24891195E12
Primary
COLCRYS

Approved Use

Colchicine is indicated for Familial Mediterranean fever (FMF) in adults and children 4 years or older

Launch Date

1.24891195E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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
0.6 mg single, oral
dose: 0.6 mg
route of administration: oral
experiment type: single
co-administered:
COLCHICINE plasma
Homo sapiens
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
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
0.6 mg single, oral
dose: 0.6 mg
route of administration: oral
experiment type: single
co-administered:
COLCHICINE plasma
Homo sapiens
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
61%
COLCHICINE serum
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
50 mg single, oral
Overdose
Dose: 50 mg
Route: oral
Route: single
Dose: 50 mg
Sources:
unknown, 42 years
n = 1
Health Status: unknown
Age Group: 42 years
Sex: M
Population Size: 1
Sources:
Other AEs: Myelosuppression...
Other AEs:
Myelosuppression (grade 4, 1 patient)
Sources:
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%)
Vomiting (13%)
Diarrhea (20%)
Injection site reactions (20%)
Myalgia (27%)
Arthralgia (7%)
Allergic reaction (7%)
Sources:
12 mg single, oral
Overdose
Dose: 12 mg
Route: oral
Route: single
Dose: 12 mg
Sources:
unknown, 56 years
n = 1
Health Status: unknown
Age Group: 56 years
Sex: M
Population Size: 1
Sources:
Other AEs: Rhabdomyolysis...
Other AEs:
Rhabdomyolysis (grade 5, 1 patient)
Sources:
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)
Epigastric pain (severe, 1 patient)
Nausea (1 patient)
Vomiting (1 patient)
Sources:
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)
Fall (serious, 2 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Myelosuppression grade 4, 1 patient
50 mg single, oral
Overdose
Dose: 50 mg
Route: oral
Route: single
Dose: 50 mg
Sources:
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
Dose: 12 mg
Route: oral
Route: single
Dose: 12 mg
Sources:
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

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical 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

PubMed

TitleDatePubMed
Rapid-onset colchicine myoneuropathy.
1992 Dec
Induced differentiation in HT29, a human colon adenocarcinoma cell line.
1999 Aug
Treatment of linear IgA bullous dermatosis of childhood with colchicine.
1999 Jan-Feb
Hypernatraemia and polyuria due to high-dose colchicine in a suicidal patient.
1999 Jun
Colchicine protects mice from the lethal effect of an agonistic anti-Fas antibody.
2000 Feb
Improvement of renal function in patients with chronic gout after proper control of hyperuricemia and gouty bouts.
2000 Nov
[Fibroblastic rheumatism: a case report].
2001 Apr
Discovery of a novel compound: insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death.
2001 Aug 3
Danggui shaoyao san improve colchichine-induced learning acquisition impairment in rats.
2001 Dec
Decreased expression of Bcl-x protein during hepatocarcinogenesis induced exogenously and endogenously in rats.
2001 Dec
The stability of cytokeratin 18 in human liver cells during colchicine-induced microtubule disruption.
2001 Jan
Developing a model of colchicine neuropathy.
2002
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
[Summary of the Dutch College of General Practitioners' "Gout" Standard].
2002 Feb 16
Colchicine myoneuropathy in a renal transplant patient.
2002 Jul
2-Alkoxycarbonylaminopyridines: inhibitors of Mycobacterium tuberculosis FtsZ.
2002 Jul
[Myopathy caused by colchicine with myotonia].
2002 Jul 16-31
Functional analysis of MRP1 cloned from bovine.
2002 Jun 19
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
Nocodazole-induced p53-dependent c-Jun N-terminal kinase activation reduces apoptosis in human colon carcinoma HCT116 cells.
2002 Nov 15
Colchicine-induced acute myopathy in a patient with concomitant use of simvastatin.
2002 Sep-Oct
Colchicine-induced rhabdomyolysis in a patient with chronic heart failure.
2003 Dec
[A case of Behçet's disease associated with neuromyopathy induced by combination therapy with colchicine and cyclosporin].
2003 Feb
Colchicine induces apoptosis in organotypic hippocampal slice cultures.
2003 Feb 28
The role of the cytoskeleton in mechanotransduction in human osteoblast-like cells.
2003 May
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
Cytoskeletal myotoxicity from simvastatin and colchicine.
2004 Dec
Effects of colchicine on liver functions of cirrhotic rats: beneficial effects result from stellate cell inactivation and inhibition of TGF beta1 expression.
2004 Jan 15
[Abdominal pain and recurrent cholestatic jaundice].
2004 Jun 9
[Experimental study on Sorbaria sorbifolia extract against chronic liver damage in rats].
2004 Oct
Monozygotic twins concordant for intestinal Behçet's disease.
2005 Apr
[Acute coronary syndrome after diclofenac induced coronary spasm].
2005 Apr
Chromosomal aberrations in lymphocytes of healthy subjects and risk of cancer.
2005 May
Expression of corticosterone-binding globulin in the rat hypothalamus.
2006 Apr
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
Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression.
2006 Jul 26
A role for mixed lineage kinases in granule cell apoptosis induced by cytoskeletal disruption.
2006 Mar
Patents

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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 Wed Jul 05 22:41:25 UTC 2023
Edited
by admin
on Wed Jul 05 22:41:25 UTC 2023
Record UNII
I59XKK41WY
Record Status Validated (UNII)
Record Version
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Name Type Language
COLCHICINE SALICYLATE
Common Name English
SALICYLATED COLCHICINE
Common Name English
Code System Code Type Description
PUBCHEM
25113322
Created by admin on Wed Jul 05 22:41:25 UTC 2023 , Edited by admin on Wed Jul 05 22:41:25 UTC 2023
PRIMARY
CAS
7541-98-2
Created by admin on Wed Jul 05 22:41:25 UTC 2023 , Edited by admin on Wed Jul 05 22:41:25 UTC 2023
SUPERSEDED
FDA UNII
I59XKK41WY
Created by admin on Wed Jul 05 22:41:25 UTC 2023 , Edited by admin on Wed Jul 05 22:41:25 UTC 2023
PRIMARY
CAS
8013-62-5
Created by admin on Wed Jul 05 22:41:25 UTC 2023 , Edited by admin on Wed Jul 05 22:41:25 UTC 2023
PRIMARY
EPA CompTox
DTXSID60230088
Created by admin on Wed Jul 05 22:41:25 UTC 2023 , Edited by admin on Wed Jul 05 22:41:25 UTC 2023
PRIMARY
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ACTIVE MOIETY