COLCHICINE

Prepared by:
ALABADO, Alyssa
DOLLETON, Rachelle
MORA, Jenver
PHARMACOLOGY
Definition and Description

A major alkaloid from Colchicium autumnale L. and found also in other Colchicum
species.
Its primary therapeutic use in the treatment of gout, but it has been used also in the
therapy of Familial Mediterranean Fever (periodic disease).
Soluble in water, freely soluble in alcohol, and slightly soluble in ether.
 DOSE

GOUT PROPHYLAXIS
Adult: 0.6 mg orally once or twice a day. Maximum dose: 1.2 mg/day
< 16 years: Not recommended

FAMILIAL MEDITERRANEAN FEVER

Adult: 1.2 mg to 2.4 mg orally daily, administered in 1 or 2 divided doses
Age: 4 to 6 years: 0.3 to 1.8 mg orally daily, administered in 1 or 2 divided doses
Age: 6 to 12 years: 0.9 to 1.8 mg orally daily, administered in 1 or 2 divided doses
Age: Older than 12 years: 1.2 to 2.4 mg orally daily, administered in 1 or 2 divided doses
Route of administration

Oral Administration
ADME PROFILE
ABSORPTION
In healthy adults, colchicine capsules when given orally reached a mean Cmax of 3 ng/mL in
1.3 h (range 0.7 to 2.5 h) after 0.6 mg single dose administration.
Absolute bioavailability is reported to be approximately 45%.

DISTRIBUTION
Colchicine has a mean apparent volume of distribution in healthy young volunteers of
approximately 5 to 8 L/kg. Colchicine binding to serum protein is about 39%, primarily
to albumin. Colchicine crosses the placenta and distributes into breast milk.
 ADME PROFILE
METABOLISM
A published in vitro human liver microsome study showed that about 16% of colchicine is
metabolized to 2-O-demethylcolchicine and 3-O-demethylcolchicine (2- and 3-DMC,
respectively) by CYP3A4.
EXCRETION
Mainly via feces (65%); via urine (10-20%)
PHARMACODYNAMICS
 MECHANISM OF ACTION

Colchicines effectiveness as a treatment for gout has been postulated to be due to its
ability to block neutrophil-mediated inflammatory responses induced by
monosodium urate crystals in synovial fluid.
Disrupts the polymerization of -tubulin into microtubules, thereby preventing the
activation, degranulation, and migration of neutrophils to sites of inflammation.

Adverse rxn: Gastrointestinal disorders

DRUG INTERACTIONS

Colchicine is a substrate of the efflux transporter P-glycoprotein (P-gp), and the CYP3A4
metabolizing enzyme.
Clarithromycin -a dual inhibitor of CYP3A4 and P-glycoprotein. The serum concentration
of Colchicine can be increased when it is combined with Clarithromycin
Erythromycin - serum concentration of Colchicine can be increased when it is combined
with Erythromycin.
Acetylsalicylic acid - serum concentration of Acetylsalicylic acid can be increased when it is
combined with Colchicine.

Patients with renal or hepatic impairment should not be given colchicine capsules with drugs
that inhibit both P-glycoprotein and CYP3A4.
Food/Alcohol interactions

Avoid alcohol
Take without regard to meals
DISEASE INTERACTIONS

Cardiac Dysfunction
Disseminated Intravascular Coagulation
Electrolyte Disturbances
Liver Disease
Renal Dysfunction
 PHARMACOKINETIC PARAMETERS

THERAPEUTIC AND TOXIC PLASMA CONCENTRATIONS: 0.5 - 2 mg

0.0003 - 0.03 mg/L
BIOAVAILABILITY : 45%

VOLUME OF DISTRIBUTION : 5 to 8 L/kg

CLEARANCE: : 0.17 L/hr/kg ( FMF patients with end-renal disease)
0.73 L/hr/kg (FMF patients with normal renal function)

HALF-LIFE: 26.6-31.2 hrs

2 hrs in patients with alcoholic cirrhosis
2.5 hours in patients with FMF.
REFERENCES

Drug Bank (2017, May 16). Colchicine. Retrived from

https://www.drugbank.ca/drugs/DB01394
Colchicine (Colchicine) Drug Information: Side Effects and Drug Interactions -
Prescribing Information at RxList. (2017). RxList. Retrieved 17 May 2017, from
http://www.rxlist.com/colchicine-drug/side-effects-interactions.htm
QUIZ

1. A major alkaloid from Colchicium autumnale L.

2. ROA for Colchicine
3. What is the half- life for Colchicine?
4. Most common SE of colchicine.
5. Give 1 example of drug interaction.