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

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 69 Target ID: CHEMBL2095182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26132075	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gout 28 Sources: https://www.drugs.com/pro/colchicine.html	Preventing		Approved 8583	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 2009
Familial mediterranean fever 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022351lbl.pdf	Primary		Approved 8583	COLCRYS Approved Use Colchicine is indicated for Familial Mediterranean fever (FMF) in adults and children 4 years or older Launch Date 2009

C_max

Value	Dose	Analyte	Population
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 population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
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
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

AUC

Value	Dose	Analyte	Population
87 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 population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
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
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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
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

F_unbound

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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2A6 626 CYP2C19 1119 CYP2E1 729 P-gp 2052

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8960070/	no
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8960070/	no
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8960070/	no
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8960070/	no
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8960070/	no
P-gp 2052	substrate 4014 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 1946	substrate 4014 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
eMolecules	1970918	https://www.emolecules.com/cgi-bin/more?vid=1970918
eMolecules	729203	https://www.emolecules.com/cgi-bin/more?vid=729203
MolPort	MolPort-001-785-612	https://www.molport.com/shop/molecule-link/MolPort-001-785-612

PubMed

Title	Date	PubMed
Colchicine-induced lesions in the rat duodenum.	1975	171611
Acute myelomonocytic leukaemia and multiple myeloma after sulphinpyrazone and colchicine treatment of gout.	1976 Jul 10	1064465
Evaluation of natural products as inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.	1991 Jan-Feb	1710653
Rapid-onset colchicine myoneuropathy.	1992 Dec	1472131
Colchicine-induced myoneuropathy in a renal transplant patient.	1992 Jun	1604496
Acute myopathy induced by colchicine in a cyclosporine treated heart transplant recipient: possible role of the multidrug resistance transporter.	1999 Aug	10455999
Induced differentiation in HT29, a human colon adenocarcinoma cell line.	1999 Aug	10413674
Treatment of linear IgA bullous dermatosis of childhood with colchicine.	1999 Jan-Feb	10028001
Hypernatraemia and polyuria due to high-dose colchicine in a suicidal patient.	1999 Jun	10383025
[Fibroblastic rheumatism: a case report].	2001 Apr	11339131
Discovery of a novel compound: insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death.	2001 Aug 3	11478917
The stability of cytokeratin 18 in human liver cells during colchicine-induced microtubule disruption.	2001 Jan	11259854
Colchicine and griseofulvin inhibit VCAM-1 expression on human vascular endothelial cells - evidence for the association of VCAM-1 expression with microtubules.	2001 Jan	11154858
Abstracts of the Fourth International Symposium on Molecular Insect Science. May 28-June 2, 2002. Tucson, Arizona, USA.	2002	15455051
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-induced myopathy with normal creatine phosphokinase level in a renal transplant patient.	2002 Dec	12399640
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
Colchicine neuromyopathy: a report of six cases.	2002 Jul-Aug	12371628
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
Nocodazole-induced p53-dependent c-Jun N-terminal kinase activation reduces apoptosis in human colon carcinoma HCT116 cells.	2002 Nov 15	12221076
Colchicine-induced acute myopathy in a patient with concomitant use of simvastatin.	2002 Sep-Oct	12410059
[A case of Behçet's disease associated with neuromyopathy induced by combination therapy with colchicine and cyclosporin].	2003 Feb	12692989
Colchicine induces apoptosis in organotypic hippocampal slice cultures.	2003 Feb 28	12576187
[Neurotoxic effects of medications: an update].	2004	15244167
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
Establishment of a P-glycoprotein substrate screening model and its preliminary application.	2004 May 1	15112361
Effects of colchicine on the maximum biliary excretion of cholephilic compounds in rats.	2004 Sep	15304119
Acute renal failure associated with an accidental overdose of colchicine.	2005 Oct	16240705
[Nephrogenic diabetes insipidus induced by colchicine--a case report].	2005 Sep	16708563
[A case report of acute neuromyopathy induced by concomitant use of colchicine and bezafibrate].	2005 Sep	16248366
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	16148013
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
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	16495211
Colchicine therapy and the cognitive status of elderly patients with familial Mediterranean fever.	2006 Jul	16889161
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
Synthesis and biological evaluation of B-ring modified colchicine and isocolchicine analogs.	2006 May 15	16504507
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.

Name

Type

Language

COLCHICINUM

Preferred Name

English

Colchicine

Official Name

English

NSC-757

Code

English

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

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

MYINFLA

Brand Name

English

COLBENEMID COMPONENT COLCHICINE

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 [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