Colchicine
Colchicine Update: 2008

https://doi.org/10.1016/j.semarthrit.2008.08.006Get rights and content

Objectives

To review recent advances in the understanding of molecular mechanisms of drug disposition and cellular mechanisms of action and targets of colchicine, and disease applications and guidelines for oral colchicine use.

Methods

Summarized and interpreted here is the pertinent English and non-English language literature on MEDLINE® since the last update of colchicine in this journal in 1998 and published up to July 2008 regarding colchicine pharmacology, toxicology, mechanisms of action, and clinical applications in gout and other medical conditions.

Results

Assessment, after review of 1512 publications, is that oral colchicine therapy is being refined by attention to novel targets such as NALP3 and pyrin. The drug has a narrow therapeutic-toxicity window, and potentially serious drug–drug interactions (eg, with clarithromycin and cyclosporine) are better recognized and therefore preventable. Reviewed here are recent advances in colchicine pharmacogenomics, and recognition of drug–drug interactions and predictors of potential toxicities, including alterations in the P-glycoprotein multidrug transporter ABCB1, cytochrome P450 3A4 isoenzyme, and hepatobiliary and renal function. Current understanding of optimization of colchicine dosing is reviewed, as are recent findings on colchicine therapy of nonrheumatic cardiovascular, hepatic, and renal diseases (eg, lowering of C-reactive protein, and treatment of acute and recurrent pericarditis). Finally, the article reviews the recent U.S. Food and Drug Administration-mandated cessation of marketing of injectable colchicine.

Conclusions

Oral colchicine has unique anti-inflammatory and antiproliferative effects with broad ramifications for rheumatic and nonrheumatic disease applications. Significant advances in the last decade have increased understanding of predictors of both colchicine efficacy and toxicity.

Section snippets

Methods

Using relevant pertinent English and non-English articles with English abstracts or English translations, found by a MEDLINE® (Medical Literature Analysis and Retrieval System Online) search and published up to July 2008 as a primary source of information, the existing literature regarding colchicines was reviewed. The focus was on colchicine pharmacology, toxicology, mechanisms of action, and clinical applications in gout and other medical conditions. Initial MEDLINE searches used the keywords

Update on Clinical Pharmacology of Colchicine

Colchicine is readily bioavailable after oral administration via uptake in the jejunum and ileum, and the lipophilic nature of colchicine allows it to be absorbed readily by multiple cell types and to bind to its primary target, tubulin (discussed below), serving as a reservoir of the drug (4). Absolute colchicine bioavailability is less than 50% (6, 7). A schematic for colchicine disposition is provided in Figure 1. In brief, colchicine is predominantly eliminated by biliary excretion and

Discussion

Despite approximately 2000 years of use, the broad effects of colchicine are only beginning to be explored for therapeutic uses beyond gout and certain other rheumatic diseases, including certain forms of pericarditis. The results of ongoing and future clinical trials for optimization of colchicine-dosing regimens should allow for safer utilization of the drug without undue loss of clinical efficacy. For example, guidelines for colchicine dosing for acute gout are being refined, with lower

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    The author has received support from VA Research Service, National Institutes of Health and is a consultant for AR Scientific, Regeneron, ARDEA, Novartis, Pfizer, TAP, Savient, BioCryst.

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