Review article Colchicine in clinical medicine. A guide for internists Giuseppe Cocco a, ⁎, David C.C. Chu b , Stefano Pandolfi a a Medical Practice, Rheinfelden, Switzerland b Medical Practice for Traditional Chinese Medicine, Basle, Switzerland abstract article info Article history: Received 9 July 2010 Received in revised form 7 September 2010 Accepted 15 September 2010 Available online 5 November 2010 Keywords: Colchicine Inflammation Familial Mediterranean Fever Behçet Pericarditis Gout Colchicine (COL) has been used in medicine for a long time. It is well recognized as a valid therapy in acute flares of gouty arthritis, familial Mediterranean fever (FMF), Behçet's disease, and recurring pericarditis with effusion. It has also been used to treat many inflammatory disorders prone to fibrosis, mostly with disappointing therapeutic results. The pharmacotherapeutic mechanism of action of COL in diverse diseases is not fully understood, thought it is known that the drug accumulates preferentially in neutrophils, and this effect is useful in FMF. COL shows a large interindividual bioavailability. Furthermore, interactions with drugs interfering with CYP3A4 dependent enzymes and P-glycoprotein occur and are clinically important. The dosage of COL must be reduced in patients with relevant hepatic and/or renal dysfunction. However, when appropriately used and contraindications have been excluded, oral COL is a safe treatment. © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. 1. Introduction Colchicine (COL) is a natural product which can be extracted from two plants of the lily family, i.e. from the genus Colchicum (usually called Colchicum autumnale) and from the Gloriosa superba. COL is frequently used in botany [1] and it is a tricyclic alkaloid (C 22 H 25 NO) which was isolated in 1820 and has a molecular mass of 399.437 [2]. The therapeutic value of COL is well established in the treatment of acute flares of gouty arthritis, familial Mediterranean fever (FMF), Behçet's disease, and recurring pericarditis with effusion. COL has also been used, mostly with limited role, in other disorders with inflammation prone to fibrosis. The review discusses the use of COL in clinical medicine, i.e. the mechanism of action, pharmacology, dosage regimens, adverse effects, toxicity (poisoning), pharmacologic interactions, and clinical indications. 2. Mechanism of action The pharmacotherapeutic mechanism of action of COL in diverse disorders is not fully understood [2–6], thought it is known that the drug accumulates preferentially in neutrophils [7], and this effect is useful in FMF. It is assumed that most therapeutic effects of the drug are related to its capacity to bind to β-tubulin, thus inhibiting self- assembly and polymerization of microtubules and interfering with several cellular functions. COL modulates the production of chemo- kines and prostanoids, inhibits neutrophil and endothelial cell adhesion molecules and eventually it decreases neutrophil degranu- lation, chemotaxis and phagocytosis, thus reducing the initiation and amplification of inflammation [3–6]. COL also inhibits uric acid crystal deposition, which is enhanced by a low pH in the tissues, probably by inhibiting oxidation of glucose and subsequent lactic acid reduction in leukocytes [3–6]. 3. Pharmacology 3.1. Pharmacokinetics After intravenous bolus injection of COL, the area under the concentration–time curve (AUC) is 61.2 ± 12.7 ng h/ml; the steady- state volume of distribution is 419 ± 95 l; the systemic clearance is 8.5± 1.8 l/h; and the terminal half-life (t½) is 58 ± 11 h [8]. COL is lipophilic and is promptly absorbed by the jejunum and ileum [8]. In healthy individuals the mean oral bioavailability of the drug is 45%, but with a range between 24 and 88% [8]. The large variations in bioavailability account for the different interindividual responses to the same dose of COL [3–6]. After oral administration in solution form, peak plasma concentrations (Cmax) of 6.50 ± 1.03 ng/ ml is reached at time (tmax) 1.07 ± 0.55 h, with a rate of 0.109± 0.024 h -1 (Cmax/AUC). Oral tablets yield similar Cmax, tmax, and Cmax/AUC values as the intravenous administration, but AUC is significantly lower [8,9]. Most subjects exhibit a secondary peak within 6 h of administration, possibly in relation to a second absorption site or enterohepatic recirculation. This second absorption process is significantly longer than the first one, and accounts for a similar amount of COL absorbed. From the multiple-dose study, a European Journal of Internal Medicine 21 (2010) 503–508 ⁎ Corresponding author. PO Box 119, Marktgasse 10A, CH-4310 Rheinfelden 1/Switzerland. Tel.: +41 61 831 45 55; fax: +41 61 833 97 56. E-mail address: praxis@cocco.ch (G. Cocco). 0953-6205/$ – see front matter © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2010.09.010 Contents lists available at ScienceDirect European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim