Colchicine

First marketed in 1921

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H25NO6
Molecular Weight	399.437
Optical Activity	( - )
Additional Stereochemistry	Yes
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0
Stereo Comments	M-helix

SHOW SMILES / InChI

Structure Search

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

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

Description
Sources: https://www.drugs.com/pro/colchicine.html

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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin 67 Target ID: CHEMBL2095182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26132075	Inhibitor 8228

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gout 28 Sources: https://www.drugs.com/pro/colchicine.html	Preventing		Approved 8360	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
Familial mediterranean fever 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022351lbl.pdf	Primary		Approved 8360	COLCRYS Approved Use Colchicine is indicated for Familial Mediterranean fever (FMF) in adults and children 4 years or older Launch Date 1.24891195E12

C_max

Value	Dose	Analyte	Population
1.68 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210942s000lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210942s000lbl.pdf	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	Analyte	Population
18.47 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210942s000lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210942s000lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
30.54 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210942s000lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210942s000lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
61% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210942s000lbl.pdf			COLCHICINE serum	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
50 mg single, oral Overdose Dose: 50 mg Route: oral Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/33128536	unknown, 42 years n = 1 Health Status: unknown Age Group: 42 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/33128536	Other AEs: Myelosuppression... Other AEs: Myelosuppression (grade 4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/33128536
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: https://pubmed.ncbi.nlm.nih.gov/30604205/	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: https://pubmed.ncbi.nlm.nih.gov/30604205/	Sources: https://pubmed.ncbi.nlm.nih.gov/30604205/
1 mg 1 times / week multiple, intravenous Dose: 1 mg, 1 times / week Route: intravenous Route: multiple Dose: 1 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/30604205	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: https://pubmed.ncbi.nlm.nih.gov/30604205	Other AEs: Nausea, Vomiting... Other AEs: Nausea (27%) Vomiting (13%) Diarrhea (20%) Injection site reactions (20%) Myalgia (27%) Arthralgia (7%) Allergic reaction (7%) Sources: https://pubmed.ncbi.nlm.nih.gov/30604205
12 mg single, oral Overdose Dose: 12 mg Route: oral Route: single Dose: 12 mg Sources: https://pubmed.ncbi.nlm.nih.gov/31348292	unknown, 56 years n = 1 Health Status: unknown Age Group: 56 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/31348292	Other AEs: Rhabdomyolysis... Other AEs: Rhabdomyolysis (grade 5, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/31348292
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: https://pubmed.ncbi.nlm.nih.gov/17692130	unhealthy, 79 years n = 1 Health Status: unhealthy Age Group: 79 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/17692130	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: https://pubmed.ncbi.nlm.nih.gov/17692130
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: https://clinicaltrials.gov/ct2/show/NCT01985425	unhealthy n = 49 Health Status: unhealthy Condition: Thoracic Surgery Population Size: 49 Sources: https://clinicaltrials.gov/ct2/show/NCT01985425	Other AEs: Acute respiratory distress syndrome, Fall... Other AEs: Acute respiratory distress syndrome (serious, 3 patients) Fall (serious, 2 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01985425

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709	substrate 1010	substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2A6 523 CYP2C19 985 CYP2E1 648 P-gp 1527

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2A6 523	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8960070/	no
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8960070/	no
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8960070/	no
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8960070/	no
CYP2E1 648	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8960070/	no
P-gp 1527	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210942s000lbl.pdf#page=2; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204820Orig1s000ClinPharmR.pdf#page=11 Page: 2.0	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). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210942s000lbl.pdf#page=2; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204820Orig1s000ClinPharmR.pdf#page=11 Page: 2.0
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210942s000lbl.pdf#page=2; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204820Orig1s000ClinPharmR.pdf#page=11 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). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210942s000lbl.pdf#page=2; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204820Orig1s000ClinPharmR.pdf#page=11 Page: 2.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:23359	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:23359
MolPort	MolPort-001-785-612	https://www.molport.com/shop/molecule-link/MolPort-001-785-612
eMolecules	1970918	https://www.emolecules.com/cgi-bin/more?vid=1970918
eMolecules	729203	https://www.emolecules.com/cgi-bin/more?vid=729203

PubMed

Title	Date	PubMed
Colchicine-induced lesions in the rat duodenum.	1975	171611
Evaluation of natural products as inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.	1991 Jan-Feb	1710653
Colchicine myopathy in a case of familial Mediterranean fever: immunohistochemical and ultrastructural study of accumulated tubulin-immunoreactive material.	1992	1575022
Serum interleukin-2 and tumor necrosis factor-alpha in primary biliary cirrhosis: decrease by colchicine and relationship to HLA-DR4.	1992 Apr	1553933
Colchicine-induced myoneuropathy in a renal transplant patient.	1992 Jun	1604496
Acute neuromyopathy after colchicine treatment.	1992 Nov	1466611
Discovery of a novel compound: insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death.	2001 Aug 3	11478917
Danggui shaoyao san improve colchichine-induced learning acquisition impairment in rats.	2001 Dec	11749816
Decreased expression of Bcl-x protein during hepatocarcinogenesis induced exogenously and endogenously in rats.	2001 Dec	11749691
Developing a model of colchicine neuropathy.	2002	11921069
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	12446362
Colchicine myopathy: a vacuolar myopathy with selective type I muscle fiber involvement. An immunohistochemical and electron microscopic study of two cases.	2002 Feb	11810174
[Summary of the Dutch College of General Practitioners' "Gout" Standard].	2002 Feb 16	11876034
Colchicine myoneuropathy in a renal transplant patient.	2002 Jul	12122515
2-Alkoxycarbonylaminopyridines: inhibitors of Mycobacterium tuberculosis FtsZ.	2002 Jul	12096015
[Myopathy caused by colchicine with myotonia].	2002 Jul 16-31	12221632
Functional analysis of MRP1 cloned from bovine.	2002 Jun 19	12067707
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	11792417
Mechanisms by which cAMP increases bile acid secretion in rat liver and canalicular membrane vesicles.	2003 Aug	12702492
[A case of Behçet's disease associated with neuromyopathy induced by combination therapy with colchicine and cyclosporin].	2003 Feb	12692989
The role of the cytoskeleton in mechanotransduction in human osteoblast-like cells.	2003 May	12774890
Exocytotic "constipation" is a mechanism of tubulin/lysosomal interaction in colchicine myopathy.	2003 May 1	12706115
Neuroprotective action of flavopiridol, a cyclin-dependent kinase inhibitor, in colchicine-induced apoptosis.	2003 Oct	12941380
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	14573738
[Neurotoxic effects of medications: an update].	2004	15244167
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	15744361
Cytoskeletal myotoxicity from simvastatin and colchicine.	2004 Dec	15389652
RLIP76 (RALBP1)-mediated transport of leukotriene C4 (LTC4) in cancer cells: implications in drug resistance.	2004 Dec 20	15386349
Severe respiratory muscle weakness related to long-term colchicine therapy.	2004 Feb	14744269
[Abdominal pain and recurrent cholestatic jaundice].	2004 Jun 9	15318531
Acute poisoning with autumn crocus (Colchicum autumnale L.).	2004 Mar 31	15088997
Myelodysplasia and acute myeloid leukaemia in a case of rheumatoid arthritis with secondary amyloidosis treated with chlorambucil.	2004 May	15656036
Establishment of a P-glycoprotein substrate screening model and its preliminary application.	2004 May 1	15112361
[Experimental study on Sorbaria sorbifolia extract against chronic liver damage in rats].	2004 Oct	15850357
Celastraceae sesquiterpenes as a new class of modulators that bind specifically to human P-glycoprotein and reverse cellular multidrug resistance.	2004 Oct 1	15466210
Effects of colchicine on the maximum biliary excretion of cholephilic compounds in rats.	2004 Sep	15304119
RhoA/ROCK and Cdc42 regulate cell-cell contact and N-cadherin protein level during neurodetermination of P19 embryonal stem cells.	2004 Sep 5	15281068
Implication of cyclin-dependent kinase 5 in the neuroprotective properties of lithium.	2005	15979805
Establishment and characterization of new cellular lymphoma model expressing transgenic human MDR1.	2005 Apr	15725475
Induction of resistance to Aplidin in a human ovarian cancer cell line related to MDR expression.	2005 Dec	16258264
Chromosomal aberrations in lymphocytes of healthy subjects and risk of cancer.	2005 May	15866756
[A case report of acute neuromyopathy induced by concomitant use of colchicine and bezafibrate].	2005 Sep	16248366
An unusual cause of renal amyloidosis secondary to gout: the first description of familial occurrence.	2006	17065112
Expression of corticosterone-binding globulin in the rat hypothalamus.	2006 Apr	16700006
Colchicine myoneuropathy in chronic renal failure patients with gout.	2006 Apr	16669978
Involvement of cytoskeleton in AhR-dependent CYP1A1 expression.	2006 Apr	16611024
Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression.	2006 Jul 26	16930453
Sweet's syndrome from an Indian perspective: a report of four cases and review of the literature.	2006 Jun	16796632
Cyclosporine not the only agent to cause Guillain-Barré-like syndrome after solid-organ transplant.	2006 Nov	17097509
Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats.	2007	17135773

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 `Thu Jul 06 00:39:59 UTC 2023` Edited by `admin` on `Thu Jul 06 00:39:59 UTC 2023`
Record UNII	SML2Y3J35T
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Colchicine

Official Name

English

NSC-757

Code

English

COLCHICINUM

Common Name

English

ACETAMIDE, N-(5,6,7,9-TETRAHYDRO-1,2,3,10-TETRAMETHOXY-9-OXOBENZO(A)HEPTALEN-7-YL)-,(S)-

Common Name

English

COLCHICINE COMPONENT OF PROBEN-C

Common Name

English

COLCHICINE [WHO-IP]

Common Name

English

(S)-N-(5,6,7,9-TETRAHYDRO-1,2,3,10-TETRAMETHOXY-9-OXOBENZO(A)HEPTALEN-7-YL)ACETAMIDE

Systematic Name

English

COLCHICINE [USP MONOGRAPH]

Common Name

English

COLBENEMID COMPONENT COLCHICINE

Common Name

English

COLCHICINE COMPONENT OF COLBENEMID

Common Name

English

COLCHICINE COMPONENT OF COL-PROBENECID

Common Name

English

Colchicine [WHO-DD]

Common Name

English

COLCHICINE [USP-RS]

Common Name

English

COLCHICINE [EP IMPURITY]

Common Name

English

COLCHCINE [VANDF]

Common Name

English

LODOCO

Brand Name

English

GLOPERBA

Brand Name

English

(-)-COLCHICINE

Common Name

English

MITIGARE COMPONENT COLCHICINE

Brand Name

English

PROBEN-C COMPONENT COLCHICINE

Common Name

English

COLCHICINUM [WHO-IP LATIN]

Common Name

English

COLCRYS

Brand Name

English

COLCHINEOS

Common Name

English

COLCHICINE [ORANGE BOOK]

Common Name

English

COLCHICINE COMPONENT OF MITIGARE

Brand Name

English

COLCHICINE [MI]

Common Name

English

COLCHICINUM [HPUS]

Common Name

English

COLCHICINE [EP MONOGRAPH]

Common Name

English

COLCHICINE [JAN]

Common Name

English

COLCHICINE [MART.]

Common Name

English

COL-PROBENECID COMPONENT COLCHICINE

Common Name

English

COLCHISOL

Common Name

English

COLCHICINE [HSDB]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QM04AC01