SEARCH · PubMed Health

Results for “Colchicine”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources

PubMed1975

Anti-prostaglandin action of colchicine.

Colchicine, given locally, inhibits urate-crystal- and CaPPD-crystal-induced inflammation. Since this inflammation is known to be mediated in part by PGE1 these observations indicate colchicine acts as an anti-PG agent. Colchicine counteracts the phlogistic action of exogenous PGE1 in both urate- and CaPPD-crystal-induced inflammation. With use of large excesses of colchicine, its anti-inflammatory action appears limited to its anti-PGE1 activity. In turn, PGE1 counteracts the antiphlogistic action of colchicine. Colchicine is less effective in reducing swelling due to CaPPD-crystals than that due to urate-crystals, a finding similar to the clinical observations that colchicine is more effective therapy for gout than for pseudogout. Some relationships are reviewed to suggest that CaPPD-crystal inflammation is a more severe membrane disorder than is urate-crystal inflammation.

Animals↗

PubMed2001

Microtubule disruption by colchicine reversibly enhances calcium signaling in intact rat cardiac myocytes.

Using the whole-cell patch-clamp configuration in rat ventricular myocytes, we recently reported that microtubule disruption increases calcium current (I(Ca)) and [Ca(2+)](i) transient and accelerates their kinetics by adenylyl cyclase activation. In the present report, we further analyzed the effects of microtubule disruption by 1 micromol/L colchicine on Ca(2+) signaling in cardiac myocytes with intact sarcolemma. In quiescent intact cells, it is possible to investigate ryanodine receptor (RyR) activity by analyzing the characteristics of spontaneous Ca(2+) sparks. Colchicine treatment decreased Ca(2+) spark amplitude (F/F(0): 1.78+/-0.01, n=983, versus 1.64+/-0.01, n=1660, recorded in control versus colchicine-treated cells; P<0.0001) without modifying the sarcoplasmic reticulum Ca(2+) load and enhanced their time to peak (in ms: 6.85+/-0.09, n=1185, versus 7.33+/-0.13, n=1647; P<0.0001). Microtubule disruption also induced the appearance of Ca(2+) sparks in doublets. These alterations may reflect RyR phosphorylation. To further investigate Ca(2+) signaling in cardiac myocytes with intact sarcolemma, we analyzed [Ca(2+)](i) transient evoked by field stimulation. Cells were loaded with the fluorescence Ca(2+) indicator, Fluo-3 cell permeant, and stimulated at 1 HZ: [Ca(2+)](i) transient amplitude was greater and its decay was accelerated in colchicine-treated, field-stimulated myocytes. This effect is reversible. When colchicine-treated myocytes were placed in a colchicine-free solution for 30 minutes, tubulin was repolymerized into microtubules, as shown by immunofluorescence, and the increase in [Ca(2+)](i) transient was reversed. In summary, we demonstrate that microtubule disruption by colchicine reversibly modulates Ca(2+) signaling in cardiac cells with intact sarcolemma.

Animals↗

PubMed1997

An evaluation of colchicine as an alternative to inhaled corticosteriods in moderate asthma. National Heart, Lung, and Blood Institute's Asthma Clinical Research Network.

Colchicine demonstrates an array of anti-inflammatory properties of potential relevance to asthma. However, the efficacy of colchicine as an alternative to inhaled corticosteroid therapy for asthma is unknown. Five centers participated in a controlled trial testing the hypothesis that in patients with moderate asthma needing inhaled corticosteroids for control, colchicine provides therapeutic benefit as measured by maintenance of control when inhaled steroids are discontinued. Subjects were stabilized on triamcinolane acetonide (800 microg daily) and then enrolled in a 2-wk run-in during which all subjects took both colchicine (0.6 mg/twice a day) and triamcinolone. At the end of the run-in, all subjects discontinued triamcinolone and were randomized to continued colchicine (n = 35) or placebo (n = 36) for a 6-wk double-blind treatment period. The treatment groups were similar in terms of disease severity. After corticosteroid withdrawal, 60% of colchicine-treated and 56% of placebo-treated subjects were considered treatment failures as defined by preset criteria. No significant difference in survival curves was found between treatment groups (log rank = 0.38). Other measures, including changes in FEV1, peak expiratory flow, symptoms, rescue albuterol use, and quality of life scores, also did not differ between groups. Of note, subjects failing treatment had significantly greater methacholine responsiveness at baseline than did survivors (PC20, 0.81+/-1.38 versus 2.11+/-2.74 mg/ml; p = 0.01). An analysis of treatment failures suggested that the criteria selected for failure reflected a clinically meaningful but safe level of deterioration. We conclude that colchicine is no better than placebo as an alternative to inhaled corticosteroids in patients with moderate asthma. Additionally, we conclude that the use of treatment failure as the primary outcome variable in an asthma clinical trial where treatment is withdrawn is feasible and safe under carefully monitored conditions.

Administration, Inhalation↗

PubMed1970

Effect of colchicine on intestinal disaccharidases: correlation with biochemical aspects of cellular renewal.

There was a significant depression of the activities of intestinal lactase, invertase, and alkaline phosphatase in rats given drinking water containing 2.5 mg of colchicine per 100 ml. Activities of intestinal maltase, aspartate transcarbamylase, and dihydroorotase were not affected by the drug. Injection of colchicine (1 mg/kg) caused depression of intestinal invertase activity within 8 hr. Investigation of the effect of colchicine on the disaccharides in vitro demonstrated that invertase and maltase were not affected by concentrations up to 125 mg/100 ml. Intestinal lactase was inhibited by concentrations exceeding 5 mg/100 ml. Calculation of the concentration of colchicine present in the intestine, after a single injection, indicated that the in vivo effect of colchicine was not due to simple enzyme inhibition. Histological examination showed an increase in crypt cells but no decrease in the length of the villi. Cellular migration along the villi, as well as activity of uridine kinase in intestinal mucosa, was increased in colchicine-treated rats. It was concluded that colchicine did not depress intestinal invertase, lactase, and alkaline phosphatase by decreasing cellular renewal, but rather it exerted its effect directly on the differentiated cells of the villus.

Alkaline Phosphatase↗

PubMed1991

Colchicine antimitosis abolishes CCl4 autoprotection.

A subtoxic dose of CCl4 is known to destroy liver microsomal cytochrome P-450 and this is widely accepted as the mechanism of CCl4 autoprotection. Circumstantial evidence suggests that while cytochrome P-450 is significantly decreased, this mechanism alone cannot explain the phenomenon of autoprotection. Previous studies have established that hepatocellular regeneration is stimulated as early as 6 hr after the administration of a low dose of CCl4. If the early phase stimulation of hepatocellular regeneration by the protective dose is indeed the mechanism of autoprotection, then ablation of this early phase of tissue healing by colchicine should result in an abolishment of autoprotection. Present studies were conducted to test this conceptual premise. The protection afforded by a low dose of CCl4 (LCCl4, 100 microliter/kg, ip) on the toxic effects of a subsequently administered moderately toxic dose of CCl4 (HCCL4, 2.5 ml/kg, ip) was established in male Sprague-Dawley rats. The protective dose provided 100% protection, whereas only 62.5% survival was observed when the corn oil vehicle was administered instead of the protective dose of LCCl4. Colchicine administration (1 mg/kg, ip in saline) 2 hr prior to the injection of LCCl4 led to a complete loss of autoprotection resulting in 100% mortality in rats given the HCCl4. Earlier studies have established that colchicine selectively suppresses the early phase of hepatocellular regeneration at 6 hr without influencing the second phase at 36-48 hr. The consequence of colchicine antimitosis on the toxicological endpoints of liver injury was evaluated by serum enzyme elevations and by histopathological examination of the liver during a time course of 6, 24, 48, 72, and 96 hr after the administration of HCCl4. In the autoprotection regime, after only a transient and modest elevation of serum alanine and aspartate transaminases, complete recovery occurred by 96 hr. Hepatocellular necrosis was consistently lower compared to all other groups. Colchicine preadministration in the autoprotection regime resulted in significantly greater and progressive elevation of the serum enzymes and a correspondingly commensurate progression of hepatic lesion. Toxic effects of HCCl4 alone were more rapidly and maximally augmented by colchicine preadministration. The role of hepatocellular regeneration in autoprotection was evaluated by 3H-thymidine incorporation in hepatocellular nuclear DNA and by morphometric estimation of mitotic index. While HCCl4 alone resulted in some stimulation of 3H-thymidine incorporation and mitosis, the regenerative activity observed with prior LCCl4 administration was remarkably greater, particularly at 48 hr. Colchicine preadministration in either of these 2 protocols decisively obtunded the stimulated regenerative activities essentially abolishing the tissue healing mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine Transaminase↗

PubMed2000

Comparison of enterotoxicity between autumn crocus (Colchicum autumnale L.) and colchicine in the guinea pig and mouse : enterotoxicity in the guinea pig differs from that in the mouse.

Autumn crocus poisoning of cattle is characterized by severe diarrhea caused by alkaloid colchicine. Previously, we examined pathologically this poisoning in cattle and reported that enterotoxic lesions were closely associated with apoptosis. To examine enterotoxicity of autumn crocus more precisely, a reproductive study was performed using guinea pigs and mice, and pathological findings associated with autumn crocus poisoning were compared with those of colchicine. Each group of guinea pigs given the bulb of autumn crocus or colchicine exhibited severe diarrhea. Histopathological findings in intoxicated guinea pigs were entirely consistent with those in the autumn crocus-poisoned cattle. In contrast, each group of mice administered with the bulb or colchicine did not develop diarrhea. Our results confirmed that the toxicity of autumn crocus bulb is attributable to the toxicity of ingredient colchicine, and revealed that the guinea pig has high reproducibility of autumn crocus poisoning in cattle and colchicine poisoning in humans. It has been reported that the physiological mechanism of the apoptotic process for eliminating the enterocytes in the mouse and rat differs from that of the guinea pig, monkey, cattle and horse. Taking the observation that the former animals do not develop diarrhea, whereas the latter animals do so in the autumn crocus or colchicine poisoning into consideration, it would seem that the species-difference in enterotoxicity of autumn crocus may be closely associated with the physiological mechanism of eliminating the effete enterocytes.

Animals↗

PubMed2001

Probable colchicine-induced neutropenia not related to intentional overdose.

OBJECTIVE: To report a case of neutropenia caused by colchicine not associated with intentional overdose or with preceding severe gastrointestinal symptoms. CASE SUMMARY: A 68-year-old white man was admitted to the hospital with intractable pain from an acute attack of gout. The patient was treated with standard doses of oral colchicine for several days. He experienced mild loose stools, but no severe diarrhea or nausea during treatment. The patient then developed severe neutropenia, with an absolute neutrophil count of 240 cells/mm3. His white blood cell count returned to normal after discontinuing colchicine and administering filgrastim. DISCUSSION: Although colchicine is commonly associated with neutropenia in cases of intentional or accidental overdose, the patient developed this adverse effect after being treated with doses commonly used for the acute treatment of gout. In addition, this patient had taken low-dose colchicine for many years without experiencing hematologic adverse effects. CONCLUSIONS: Colchicine is often an attractive alternative to nonsteroidal antiinflammatory agents for the treatment of gout, especially in patients at risk for renal impairment or gastropathy. Our case illustrates that colchicine treatment can cause hematologic adverse effects; the clinician should monitor cell counts in patients receiving this agent, especially at the higher doses used for acute treatment of gout.

Aged↗

PubMed2002

Colchicine-induced rhabdomyolysis.

OBJECTIVE: To report a case of rhabdomyolysis occurring during treatment with colchicine. CASE SUMMARY: A 44-year-old African American man was admitted to the hospital due to persistent diarrhea, vomiting, and diffuse weakness. Past medical history was significant for renal failure requiring peritoneal dialysis, gout, and a new skin lesion. Approximately 2 months prior to admission, he had been started on colchicine and allopurinol. Creatine kinase concentration on admission was >14 000 U/L. Liver function tests were elevated 5 times the upper limit of normal. Colchicine was discontinued on admission. Creatine kinase concentrations decreased significantly, and strength and ambulation improved throughout hospitalization. DISCUSSION: Colchicine was thought to be the causative factor for rhabdomyolysis in conjunction with chronic renal failure and elevated liver function tests. After discontinuation of colchicine, creatinine kinase concentrations declined and the patient's ability to walk improved. Limited case reports of colchicine-induced rhabdomyolysis have been published. CONCLUSIONS: Chronic renal failure in conjunction with elevated liver function tests appear to increase the possibility of colchicine-induced toxicity, specifically, rhabdomyolysis.

Adult↗

PubMed2003

Colchicine-induced myopathy in a teenager with familial Mediterranean fever.

OBJECTIVE: To report a case of colchicine-induced myopathy in a teenager with familial Mediterranean fever (FMF). CASE SUMMARY: A 15-year-old boy of Turkish origin, diagnosed as having FMF at the age of 14 years, was treated with colchicine 1.5 mg/d. He had experienced only 2 mild peritonitis attacks with fever within 1 year. The patient used the recommended dose regularly, and he described progressive proximal muscle weakness and generalized myalgias, which started 1 month before presentation. Physical examination showed proximal muscle weakness in his arms and legs. Laboratory tests revealed elevated serum creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. All other laboratory values were within normal range. Electromyographic investigation revealed a myopathic pattern in proximal muscles without any neuropathic changes. A biopsy of the deltoid muscle showed vacuolar degeneration of striated muscle fibers with no inflammatory findings. DISCUSSION: Colchicine, the most important drug in treatment of FMF, can cause myopathy in patients with impaired renal and hepatic function. In our patient, an objective causality scale showed that therapeutic doses of colchicine for FMF were the definite cause of myopathy, even though his renal and hepatic function were normal. The treatment of FMF attacks in patients who cannot use colchicine is an important problem. There are insufficient data about the use of immunosuppressive agents in the treatment of FMF attacks; however, we now successfully control the attacks with colchicine 0.5 mg/d and azathioprine 2 mg/kg/d. CONCLUSIONS: Colchicine-induced myopathy should be excluded in patients with FMF who present with generalized muscle weakness. Clinicians should be aware that myopathy can occur in patients with FMF who have normal renal and hepatic function.

Adolescent↗

PubMed2006

Rhabdomyolysis in a patient treated with colchicine and atorvastatin.

OBJECTIVE: To report a case of severe rhabdomyolysis that developed after administration of atorvastatin to a patient receiving regular colchicine treatment. CASE SUMMARY: A 45-year-old man with nephrotic syndrome and amyloidosis presented with dyspnea, altered mentation, and severe fatigue. He had been taking colchicine 1.5 mg/day for amyloidosis for 3 years without adverse effects. Atorvastatin 10 mg/day was prescribed for hypercholesterolemia one month prior to admission. After 2 weeks of atorvastatin treatment, he began to experience myalgia and reduced muscle strength. The creatinine and creatine kinase concentrations on admission were 8.1 mg/dL and 9035 U/L, respectively. The patient was diagnosed with rhabdomyolysis with the findings of myoglobinuric, oliguric acute renal failure, and more than 50-fold elevated creatine kinase concentration. His muscle strength improved after withdrawal of atorvastatin and colchicine. However, he died because of nosocomial pneumonia that developed during his hospital stay. The Naranjo probability scale indicated that atorvastatin and colchicine were probable causes of rhabdomyolysis. DISCUSSION: Atorvastatin and colchicine have well-known myotoxic adverse effects. Despite atorvastatin's proven safety, its use with certain drugs, such as colchicine, makes it a potential myotoxic drug. This might be because concomitant administration of P-glycoprotein substrates, such as statins, and colchicine, which is a P-glycoprotein inhibitor, modifies pharmacokinetics by increasing bioavailability and organ uptake of the substrates, leading to more adverse reactions and toxicities. CONCLUSIONS: We recommend checking the creatine kinase level one week after prescribing 2 or more potentially myotoxic drugs concomitantly, after dose increase of a myotoxic drug, or after prescribing a new drug to a patient already using other myotoxic agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1978

Impairment of glucose-induced insulin secretion and glucose tolerance during colchicine treatment.

The effect of acute and chronic colchicine treatment on glucose-induced immunoreactive insulin secretion and glucose tolerance was examined in fasting, unanesthetized, and unrestrained rats with indwelling jugular vein and aortic catheters. In the first study, intravenous glucose tolerance tests were performed by rapidly administering a glucose pulse (150 mg. intravenously) one hour after acute treatment with colchicine (0.5 mg. per kilogram of body weight, intravenously) or vehicle (control). Acute colchicine treatment caused significant suppression of glucose-induced insulin secretion and also markedly impaired glucose disappearance rates. In the second study, chronic colchicine treatment (in the lower dose of 0.2 mg. per kilogram of body weight, intraperitoneally, daily for 10 days) caused significant suppression of biphasic insulin secretion in response to a primed-constant glucose infusion (150 mg. of glucose pulse followed by 6 mg. per minute constant glucose infusion for 60 minutes) as compared with control rats (vehicle injection, intraperitoneally, daily for 10 days). Due to this marked decrease in biphasic insulin secretion, serum glucose concentrations were significantly higher between 10 and 45 minutes in the colchicine-treated rats than in the control rats. Therefore, acute and chronic colchicine treatment causes marked inhibition of glucose-induced insulin secretion and impairment of glucose tolerance in the intact rat. These observations suggest there is a need to evaluate carbohydrate metabolism in patients receiving colchicine treatment.

Animals↗

PubMed1994

Plasma kinetics and biliary excretion of colchicine in patients with chronic liver disease after oral administration of a single dose and after long-term treatment.

Plasma kinetics and biliary excretion of colchicine in patients with chronic liver disease were evaluated after oral administration of a single dose and after long-term treatment. A single oral dose of 1 mg colchicine led to a mean peak concentration of 3.60 +/- 1.04 ng/ml at a peak time of 2.16 +/- 0.34 h and a mean area under the plasma concentration time curve, extrapolated from time 0 to infinity, of 24.90 +/- 8.47 ng.h/ml. Comparable values were obtained after repeated administration. Distribution half-life was 2.83 +/- 0.74 h, and terminal plasma half-life was 9.81 +/- 2.08 h; the mean apparent volume of distribution and the mean apparent plasma clearance were 1448 +/- 4061 and 175.3 +/- 47.6 1/h, respectively. Colchicine concentrations in bile (2025 +/- 1368 ng/ml) were clearly higher than in plasma. Long-term treatment with colchicine (1 mg/day) in patients with various stages of primary biliary cirrhosis (PBC) was associated with colchicine concentrations varying from < 0.15 to 2.0 ng/ml, with a slight tendency to higher concentrations in PBC stages III-IV than I-II. Although about 20% of colchicine is excreted in bile within 24 h, accumulation of colchicine may appear only in patients with advanced liver disease and cholestasis.

Administration, Oral↗

PubMed1994

A clinical study of colchicine in childhood asthma.

A double-blind, randomized, crossover study was done to determine the efficacy of colchicine in 30 atopic children with moderately severe asthma. A constant dose of sustained-release theophylline and salbutamol by inhalation, as needed, was administered to all patients. Compared to placebo, colchicine, 0.5 mg twice daily, significantly reduced morning tightness and nocturnal asthma score. There was, however, no significant difference between colchicine and placebo for cough, daytime asthma, or daily combined symptom scores for each patient. Colchicine did not significantly decrease beta-2 agonist inhaler use when compared with placebo. Similarly, there was no statistically significant difference between placebo and colchicine therapy as far as pulmonary function tests and peak flow reversibility were concerned. Thus, colchicine administered for 4 weeks demonstrated insufficient antiasthma activity. Colchicine-induced clinical improvement that was reported in a previous study may be due to selection of patients with mild asthma symptoms. However, our group, comprised of moderately severe asthmatic patients, did not show a satisfactory clinical response.

Albuterol↗

PubMed1982

Bovine mammary involution following intramammary infusion on colchicine and endotoxin at drying off.

Effects of intramammary infusion of colchicine, endotoxin, and colchicine in combination with endotoxin on mammary involution were studied on 25 dairy cows in late lactation. Both quarters of right udder halves were infused at or near drying off while left udder halves received no infusion. Samples of mammary secretion were obtained 1 day prior to drying off, at drying off, and .5, 1, 2, 3, and 7 days post drying off. Mammary secretion obtained during the early dry period from udder halves infused with colchicine or colchicine and endotoxin at or near drying off had elevated somatic cells, lactoferrin, serum albumin, immunoglobulin G, and pH as compared to left untreated udder halves. Citrate, molar ratio of citrate to lactoferrin, and the index of selective accumulation of immunoglobulin G were lower in infused than uninfused udder halves. Fluid volume removed from udders at 7 days involution was 40% less in udder halves infused with colchicine or colchicine and endotoxin as compared to uninfused udder halves. Intramammary infusion of colchicine and endotoxin at drying off accelerates bovine mammary involution.

Animals↗

PubMed1997

Acute myopathy induced by colchicine in a cyclosporine-treated renal transplant recipient--a case report and review of the literature.

We report a case of colchicine-induced myopathy related to short-term, customary administration of colchicine. A 49-year-old male was admitted because of muscle weakness and myalgia that had developed 10 days previously. He had received renal transplantation 5 years previously and took cyclosporine as an immunosuppressant. Two weeks before admission, gout was developed and he took colchicine (1.2 mg b.i.d) by himself for three days. Colchicine-induced myopathy was clinically suspected, and colchicine intake was stopped immediately. After that, clinical symptoms gradually improved and serum muscle enzyme returned to normal. In this case, mild renal dysfunction and drug interaction between cyclosporine and colchicine wee suggested to be the precipitating factors of colchicine-induced myopathy.

Colchicine↗

PubMed2005

Colchicine sensitizes human hepatocellular carcinoma cells to damages caused by radiation.

AIM: We studied the effect of colchicine combined with radiation on the survival of human hepatocellular carcinoma (HCC) HA22T/VGH cells. METHODS: Twenty-four hours after treatment with 0-8 ng/mL colchicine, HA22T/VGH cells were irradiated at various doses (0, 1, 2, 4, and 8 Gy). Colony assay was performed to assess the surviving cell fraction. Survival curves were fitted by using a linear-quadratic model to estimate the sensitizer enhancement ratio (SER). Flow cytometry was used for cell cycle analysis. RESULTS: Colchicine at lower concentrations (1 and 2 ng/mL) had obvious synergy with radiation to inhibit HCC cell growth, whereas higher concentrations (4 and 8 ng/mL) had only additive effect to radiation. Pretreatment with 1 and 2 ng/mL colchicine for 24-h enhanced cell killing by radiation with SERs of 1.21 and 1.53, respectively. G(2)/M arrest was only observed with higher colchicine doses (8 and 16 ng/mL) after 24-h treatment; this effect was neither seen with lower doses (1, 2, and 4 ng/mL) nor with any dose after only 1 h of treatment. CONCLUSION: Our results suggest that colchicine has potential as an adjunct to radiotherapy for HCC treatment. Lower doses of colchicine possess radiosensitizing effects via some mechanism other than G(2)/M arrest. Further study is necessary to elucidate the mechanism.

Carcinoma, Hepatocellular↗

PubMed1977

Podophyllotoxin as a probe for the colchicine binding site of tubulin.

The binding of [3H]podophyllotoxin to tubulin, measured by a DEAE-cellulose filter paper method, occurs with an affinity constant of 1.8 X 10(6) M-1 (37 degrees at pH 6.7). Like colchicine, approximately 0.8 mol of podophyllotixin are bound per mol of tubulin dimer, and the reaction is entropy-driven (43 cal deg-1 mol-1). At 37 degrees the association rate constant for podophyllotoxin binding is 3.8 X 10(6) M-1 h-1, approximtaely 10 times higher than for colchicine; this is reflected in the activation energies for binding which are 14.7 kcal/mol for podophyllotoxin and 20.3 kcal/mol for colchicine. The dissociation rate constant for the tubulin-podophyllotoxin complex is 1.9 h-1, and the affinity constant calculated from the ratio of the rates is close to that obtained by equilibrium measurements. Podophyllotxin and colchicine are mutually competitive inhibitors. This can be ascribed to the fact that both compounds have a trimethoxyphenyl ring and analogues of either compound with bulky substituents in their trimethoxyphenyl moiety are unable to inhibit the the binding of either of the two ligands. Tropolone, which inhibits colchicine binding competitively, has no effect on the podophyllotoxin/tubulin reaction. Conversely, podophyllotoxin does not influence tropolone binding. Moreover, the tropolone binding site of tubulin does not show the temperature and pH lability of the colchicine and podophyllotoxin domains, hence this lability can be ascribed to the trimethoxyphenyl binding region of tubulin. Since podophyllotoxin analogues with a modified B ring do not bind, it is concluded that both podophyllotoxin and colchicine each have at least two points of attachment to tubulin and that they share one of them, the binding region of the trimethoxyphenyl moiety.

Animals↗

PubMed1992

Pharmacokinetics of colchicine: a review of experimental and clinical data.

Thanks to the development of a sensitive and specific radioimmunoassay for colchicine, the pharmacokinetics of colchicine is now well-established after single oral doses. Absorption is characterized by a zero-order rate constant while disposition appears biexponential with a rapid distribution phase (t1/2 = 1.8 h) and a long elimination phase (t1/2 = 20 h). All studies confirm the large total body clearance (35 l/h) predominantly by the extrarenal route and the large distribution volume (700 l). Further studies need to be performed to investigate colchicine absorption and to describe the metabolic pathway of the drug. To date, relationships between colchicine plasma levels and pharmacological effects have not been defined. Monitoring of plasma levels in patients with familial Mediterranean fever should improve treatment with colchicine. However, the therapeutic range has not been precisely determined. The use of colchicine in the treatment of liver cirrhosis and primary biliary cirrhosis is a recent development; so, assuming that a large part of total body clearance depends on hepatic function, the influence of hepatic diseases on colchicine disposition needs to be investigated in order to define the most appropriate therapeutic dosing.

Administration, Oral↗