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Dalbeth N.,University of Auckland | Lauterio T.J.,URL Pharma Inc. | Wolfe H.R.,Kyowa Kirin Pharma Inc
Clinical Therapeutics | Year: 2014

Purpose: The aims of this article were to systematically review the literature about the mechanism of action of colchicine in the multimodal pathology of acute inflammation associated with gout and to consider the clinical utility of colchicine in other chronic inflammatory diseases. Methods: The English-language literature on PubMed was searched for articles published between 1990 and October 2013, with a cross-reference to citations across all years. Relevant articles pertaining to the mechanism of action of colchicine and the clinical applications of colchicine in gout and other inflammatory conditions were identified and reviewed. Findings: The molecular pathology of acute inflammation associated with gouty arthritis involves several concurrent pathways triggered by a variety of interactions between monosodium urate crystals and the surface of cells. Colchicine modulates multiple pro- and antiinflammatory pathways associated with gouty arthritis. Colchicine prevents microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis. Many of these cellular processes can be found in other diseases involving chronic inflammation. The multimodal mechanism of action of colchicine suggests potential efficacy of colchicine in other comorbid conditions associated with gout, such as osteoarthritis and cardiovascular disease. Implications: Colchicine has multiple mechanisms of action that affect inflammatory processes and result in its utility for treating and preventing acute gout flare. Other chronic inflammatory diseases that invoke these molecular pathways may represent new therapeutic applications for colchicine. © 2014 The Authors. Source


Dalbeth N.,University of Auckland | Lauterio T.J.,URL Pharma Inc. | Wolfe H.R.,Kyowa Hakko Kirin Pharma Inc.
Clinical Therapeutics | Year: 2014

Purpose The aims of this article were to systematically review the literature about the mechanism of action of colchicine in the multimodal pathology of acute inflammation associated with gout and to consider the clinical utility of colchicine in other chronic inflammatory diseases.Methods The English-language literature on PubMed was searched for articles published between 1990 and October 2013, with a cross-reference to citations across all years. Relevant articles pertaining to the mechanism of action of colchicine and the clinical applications of colchicine in gout and other inflammatory conditions were identified and reviewed.Findings The molecular pathology of acute inflammation associated with gouty arthritis involves several concurrent pathways triggered by a variety of interactions between monosodium urate crystals and the surface of cells. Colchicine modulates multiple pro- and antiinflammatory pathways associated with gouty arthritis. Colchicine prevents microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis. Many of these cellular processes can be found in other diseases involving chronic inflammation. The multimodal mechanism of action of colchicine suggests potential efficacy of colchicine in other comorbid conditions associated with gout, such as osteoarthritis and cardiovascular disease.Implications Colchicine has multiple mechanisms of action that affect inflammatory processes and result in its utility for treating and preventing acute gout flare. Other chronic inflammatory diseases that invoke these molecular pathways may represent new therapeutic applications for colchicine. © 2014 The Authors. Published by Elsevier HS Journals, Inc. Source


Wason S.,Mutual Pharmaceutical Company | Wason S.,Lexicon Pharmaceuticals Inc. | Mount D.,Harvard University | Faulkner R.,Mutual Pharmaceutical Company | Faulkner R.,URL Pharma Inc.
Clinical Drug Investigation | Year: 2014

Results: Colchicine exposure was similar for subjects with normal renal function, mild impairment, or ESRD prior to and during hemodialysis (24.7–31.7 ng·h/mL), but was up to twofold higher in subjects with moderate or severe renal impairment (48.9 and 48.0 ng·h/mL, respectively). A very small amount of the colchicine dose (mean of 5.2 %) was recovered in dialysate.Background and Objective: The effect of renal impairment on colchicine pharmacokinetics in patients with chronic kidney disease (CKD) has not been studied previously. We evaluated the effect of renal impairment on colchicine pharmacokinetics in patients with CKD.Methods: The pharmacokinetics and safety of a single, oral 0.6-mg dose of colchicine was evaluated in an open-label study in eight healthy subjects with normal renal function; eight subjects each with mild, moderate, or severe renal impairment; and eight subjects with end-stage renal disease (ESRD) who received a single dose prior to receiving, and again following, hemodialysis.Conclusions: It appears that patients with mild or moderate renal impairment or those actively receiving hemodialysis do not show accumulation of colchicine, whereas those with severe renal impairment show a doubling of exposure. All patients with renal impairment taking colchicine should be closely monitored, especially as many patients taking colchicine often have other comorbidities and may be taking other medications. © 2014, Springer International Publishing Switzerland. Source


Terkeltaub R.A.,University of California at San Diego | Furst D.E.,University of California at Los Angeles | Bennett K.,Salamandra LLC | Kook K.A.,Salamandra LLC | And 2 more authors.
Arthritis and Rheumatism | Year: 2010

Objective. Despite widespread use of colchicine, the evidence basis for oral colchicine therapy and dosing in acute gout remains limited. The aim of this trial was to compare low-dose colchicine (abbreviated at 1 hour) and high-dose colchicine (prolonged over 6 hours) with placebo in gout flare, using regimens producing comparable maximum plasma concentrations in healthy volunteers. Methods. This multicenter, randomized, doubleblind, placebo-controlled, parallel-group study compared self-administered low-dose colchicine (1.8 mg total over 1 hour) and high-dose colchicine (4.8 mg total over 6 hours) with placebo. The primary end point was ≥50% pain reduction at 24 hours without rescue medication. Results. There were 184 patients in the intent-totreat analysis. Responders included 28 of 74 patients (37.8%) in the low-dose group, 17 of 52 patients (32.7%) in the high-dose group, and 9 of 58 patients (15.5%) in the placebo group (P = 0.005 and P = 0.034, respectively, versus placebo). Rescue medication was taken within the first 24 hours by 23 patients (31.1%) in the low-dose group (P = 0.027 versus placebo), 18 patients (34.6%) in the high-dose group (P = 0.103 versus placebo), and 29 patients (50.0%) in the placebo group. The low-dose group had an adverse event (AE) profile similar to that of the placebo group, with an odds ratio (OR) of 1.5 (95% confidence interval [95% CI] 0.7-3.2). High-dose colchicine was associated with significantly more diarrhea, vomiting, and other AEs compared with low-dose colchicine or placebo. With high-dose colchicine, 40 patients (76.9%) had diarrhea (OR 21.3 [95% CI 7.9-56.9]), 10 (19.2%) had severe diarrhea, and 9 (17.3%) had vomiting. With low-dose colchicine, 23.0% of the patients had diarrhea (OR 1.9 [95% CI 0.8-4.8]), none had severe diarrhea, and none had vomiting. Conclusion. Low-dose colchicine yielded both maximum plasma concentration and early gout flare efficacy comparable with that of high-dose colchicine, with a safety profile indistinguishable from that of placebo. © 2010, American College of Rheumatology. Source


Trademark
URL Pharma Inc. | Date: 2012-10-23

medicines and medicaments for the treatment and prevention of malaria, blood disorders, namely, dyslipidemias, rheumatic disorders, inflammatory disorders, metabolic disorders, namely, gout and familial Mediterranean fever; a full line of prescription and non-prescription pharmaceuticals, medicines and medicaments.

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