Colchicine update: 2008.
OBJECTIVE
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.
Terkeltaub
Robert A
RA
VA Medical Center, San Diego, CA 92161, USA. rterkeltaub@ucsd.edu
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism; D000284:Administration, Oral; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D003078:Colchicine / Q000493:pharmacokinetics* / Q000627:therapeutic use* / Q000633:toxicity; D000075202:Contraindications; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D006074:Gout Suppressants / Q000493:pharmacokinetics* / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D007275:Injections, Intravenous; D016239:MEDLINE; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010493:Pericarditis / Q000188:drug therapy; D017410:Practice Guidelines as Topic; D000071198:Pyrin
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D006074:Gout Suppressants; C000604192:MEFV protein, human; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D000071198:Pyrin; D051544:Cytochrome P-450 CYP3A; D003078:Colchicine