Colchicine plays an important role in the treatment of gout and some other diseases. Besides gastrointestinal symptoms, myopathy has been reported as a rare side effect of colchicine in some patients. We report a case of myopathy in a patient with chronic kidney disease caused by high-dose colchicine, and then review literature on colchicine-induced myopathy, so as to provide some experience for the clinical diagnosis, treatment and medication safety. A 51-year-old male patient with 10 years of gout and 5 years of chronic kidney disease history and irregular treatment was admitted to the hospital with complaint of recurrent left wrist arthralgia and emerging lower extremities myalgia after intake of 40-50 mg colchicine in total within 20 days. Laboratory examinations showed significantly increased creatine kinase (CK) and then colchicine-induced myopathy was diagnosed preliminarily. After withdrawl of colchicine and implementation of hydration, alkalization and intramuscular injection of compound betamethasone, the symptoms of arthralgia and myalgia were relieved within 3 days and CK decreased to normal range gradually. According to literature reports, colchicine related myopathy was mostly characterized by proximal myasthenia and myalgia, accompanied by elevated CK level, which usually occurred days to weeks after initial administration of colchicine at the usual dosage in patients with renal impairment or a change in the underlying disease state in those receiving long-term therapy, and the features might remit within three to four weeks after the drug was discontinued. Electromyography of proximal muscles showed myopathy marked by abnormal spontaneous activity and muscle pathology waa marked by accumulation of lysosomes and autophagic vacuoles. Chronic kidney disease, liver cirrhosis, higher colchicine dose and concomitant cytochrome P450 3A4 (CYP3A4) inhibitors were associated with increased risk of myo-pathy. Based on the similar efficacy and lower adverse reaction rate compared with larger dosage, small dose of colchicine was recommended by many important current guidelines and recommendations in the treatment of gout. In consideration of potential risks, colchicine should be used with caution in patients with kidney or liver impairment, and in those taking CYP3A4 or P-glycoprotein inhibitors. For those patients, the drug dose should be adjusted and the latent adverse reactions should be monitored carefully.
Colchicine/adverse effects* ; Gout/drug therapy* ; Humans ; Kidney ; Male ; Middle Aged ; Muscular Diseases/chemically induced* ; Renal Insufficiency, Chronic/complications*

OBJECTIVETo investigate the effect of microtubule depolymerization on mitochondria damage in rat myocardiocytes early after hypoxia.

METHODSMyocardiocytes from Wistar rats were isolated according to routine procedure, and they were randomly divided into control group, depolymerization group (with treatment of 4 micromol/L colchicines in the culture medium), hypoxia group, hypoxia and depolymerization group (with treatment of 4 micromol/L colchicines in the culture medium combined with low oxygen tension). The changes in distribution of the mitochondria were examined with laser confocal microscopy, the morphology and the structure of mitochondria was observed by transmission electron microscope, the respiration control ratio (RCR) was determined by respirometer, and the content of adenosine triphosphate (ATP) in endochylema was detected with liquid chromatograph at 20, 30, 60 post-hypoxia minutes (PHM).

RESULTSIn control group, the mitochondria was in granular form, with regular arrangement, while mild changes were observed in depolymerization group. At 20, 30, and 60 PHM, the disarrangement in distribution and morphologic damage were aggravated in hypoxia depolymerization group, and the RCR (1.58 +/- 0.37, 1.51 +/- 0.32, 1.12 +/- 0.11, respectively) were evidently lower than those in hypoxia group (3.85 +/- 0.56, 2.98 +/- 0.44, 1.79 +/- 0.73, respectively, P < 0.01). The content of ATP showed the same tendency at the same time-points (419 +/- 83, 326 +/- 73, 295 +/- 58 ng/mg) compared with hypoxia depolymerization group [(475 +/- 68, 397 +/- 59, 336 +/- 67 ng/mg) in hypoxia group].

CONCLUSIONThe disarrangement in distribution of mitochondria, as well as the damage in mitochondrial structure, respiratory, function and energy metabolism, can be aggravated by microtubule depolymerization after hypoxia, which indicates that microtubule depolymerization plays an important role in the mitochondria damage.

Animals ; Cell Hypoxia ; Cells, Cultured ; Colchicine ; adverse effects ; Disease Models, Animal ; Hypoxia ; pathology ; Microtubules ; pathology ; Mitochondria, Heart ; drug effects ; pathology ; Random Allocation ; Rats ; Rats, Wistar

Failure of a glaucoma filtering surgery mainly results from scarring at the filtering wound. Postoperative proliferation of fibroblasts plays an important role in scar tissue formation. Colchicine is a cytoplasmic microtu bule inhibitor capable of inhibiting fibroblast proliferation. The effect of colchicine on fibroblast proliferation at the filtering wound after fiItering surgery was investigated. Posterior lip sclerectomies were performed in each eye of albino rabbits. Under the topical or oral administration of colchicine, intracular pressure, conjunctival fibrosis, histologic finding, and drug toxicity were examined postoperatively. Compared to the untreated groups, reductions of intraocular pressure and conjunctival fibrosis in colchicine-treated groups after filtering surgery were statistically significant(p<0.05), and above changes in the topical administration group were more significant than in the oral administration group(p<0.05). Histologically, reductions of active fibroblasts and collagen fibers at the filltering wound and the subconjunctival area were seen in colchicine-treated eyes. Above findings were more prominent in the topical administration group. There were no ocular and systemic toxicities in both groups. The above results suggest that administration of colchicine, especially topical administration, can increase the success rate of filtering surgery.
Administration, Oral ; Administration, Topical ; Cicatrix ; Colchicine* ; Collagen ; Cytoplasm ; Drug-Related Side Effects and Adverse Reactions ; Fibroblasts* ; Fibrosis ; Filtering Surgery* ; Glaucoma* ; Intraocular Pressure ; Lip ; Rabbits ; Wounds and Injuries

OBJECTIVETo study the effect of anticolchicine cytotoxicity of Dan Gua-Fang, a Chinesea Chinese), a Chinese herbal compound prescription on endothelial cells of vein (ECV304) cultivated in mediums of different glucose concentrations as well as the proliferation of those cells in the same conditions, in order to reveal the value of Dan Gua-Fang in preventing and treating endothelial damage caused by hyperglycemia in diabetes mellitus.

METHODSThe research was designed as three stages. The growing state and morphological changes were observed when ECV304 were cultivated in the culture mediums, which have different glucose concentrations with or without Dan Gua-Fang and at the same time with or without colchicine.

RESULTS(1) Dan Gua-Fang at all concentrations reduced the floating cell population of ECV304 cultivated in hyperglycemia mediums. (2) Dan Gua-Fang at all concentrations and hyperglycemia both had a function of promoting "pseudopod-like" structure formation in cultivated ECV304, but the function was not superimposed in mediums containing both hyperglycemia and Dan Gua-Fang. (3) Colchicine reduced and even vanished the "pseudopod-like" structure of the endotheliocyte apparently cultivated in mediums of hyperglycemia or with Dan Gua-Fang. The "pseudopod-like" structure of the endotheliocyte emerged quickly in Dan Gua-Fang groups after colchicine was removed, but it was not the case in hyperglycemia only without Dan Gua-Fang groups. (4) Dan Gua-Fang reduced the mortality of cells cultivated in mediums containing colchicine. The cell revived to its normal state fast after colchicine was removed.

CONCLUSIONDan Gua-Fang has the functions of promoting the formation of cytoskeleton and fighting against colchicine cytotoxicity.

Cell Culture Techniques ; Cell Line ; Cell Shape ; drug effects ; Colchicine ; adverse effects ; antagonists & inhibitors ; Culture Media ; adverse effects ; pharmacology ; Cytoprotection ; drug effects ; Cytotoxins ; adverse effects ; antagonists & inhibitors ; Drug Antagonism ; Drug Combinations ; Drug Evaluation, Preclinical ; Drug Synergism ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; Endothelial Cells ; drug effects ; physiology ; Glucose ; pharmacology ; Humans ; Umbilical Veins ; cytology ; drug effects ; Up-Regulation

Colchicine-induced leukopenia usually occurrs in intentional or accidental overdoses or inappropriate use in combination with intravenous and oral colchine; however, there have been several reports of hematologic toxicity in short-term and small-dose colchicine medication courses. We present two cases of leukopenia induced by colchicine use concurrent with immunosuppressants in Behcet's disease. We postulate that the mechanism of colchicine-induced leukopenia might be the destruction of circulating leukocytes and an inhibition of leukocyte production by the immediate and direct toxic effect of colchicine on idiosyncrasies unique to each patient. The concurrently administered immunosuppressant might decrease the threshold for hematologic toxicity of colchicine in the leukocytes and their precursor cells.
Aged ; Behcet Syndrome/*drug therapy ; Blood Cell Count ; Colchicine/*adverse effects/*therapeutic use ; Female ; Humans ; Immunosuppressive Agents/*adverse effects/*therapeutic use ; Leukopenia/*chemically induced ; Middle Aged ; Time Factors ; Treatment Failure

INTRODUCTIONIn spite of being the fastest acting drug available for the control of an acute gout attack, colchicine is generally considered a last alternative in gout therapy. This is mainly due to the severe adverse effects associated with its administration through the enteral and parenteral routes, as well as its high risk/benefit ratio. The preparation of dosage forms of colchicine that can be administered by alternative routes is therefore a beneficial exercise. Among the formulable substitute dosage forms of colchicine, its ointment seems to be the best option available due to its ability to deliver the drug transdermally as well as its ease of preparation and evaluation. In this study, we prepared and tested 0.2% and 0.5% colchicine ointments for their effectiveness in delivering colchicine transdermally.

METHODSColchicine ointment was prepared using a self-formulated water-in-oil type of emulsion ointment base, with the colchicine dissolved in the water portion of the ointment base. In vitro drug release studies were carried out using the Franz diffusion test apparatus and an ultraviolet (UV)-visible spectrophotometer was used to quantify the drug in the samples. Rabbits were used as test animals for in vivo studies and the blood samples were analysed using the UV-visible spectrophotometer.

RESULTSColchicine was found to be well-absorbed transdermally, although absorption was not 100%. No side effects were associated with its 0.2% formulation.

CONCLUSIONOintments containing colchicine in low concentrations may be a feasible and effective treatment option for the prevention and treatment of acute gout attacks.

Administration, Cutaneous ; Animals ; Chemistry, Pharmaceutical ; Colchicine ; administration & dosage ; adverse effects ; Diffusion ; Dose-Response Relationship, Drug ; Gout ; drug therapy ; Hydrogen-Ion Concentration ; Ointments ; Pharmaceutical Preparations ; chemistry ; Rabbits ; Skin ; drug effects ; Solubility ; Spectrophotometry, Ultraviolet ; Time Factors