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At least 19 recordsLinked to original sources
PubMed1992

Mechanism of inhibition of microtubule polymerization by colchicine: inhibitory potencies of unliganded colchicine and tubulin-colchicine complexes.

The tubulin-colchicine binding reaction appears to involve a number of intermediate steps beginning with rapid formation of a transient preequilibrium complex that is followed by one or more slow steps in which conformational changes in tubulin and colchicine lead to formation of a poorly reversible final-state complex. In the present study, we investigated the relative ability of unliganded colchicine and preformed final-stage tubulin-colchicine complex to incorporate at microtubule ends and to inhibit addition of tubulin at the net assembly ends of bovine brain microtubules in vitro. Addition of 0.1 microM final-stage tubulin-colchicine complex to suspensions of microtubules at polymer-mass steady-state resulted in rapid incorporation of one to two molecules of tubulin-colchicine complex per microtubule net assembly end concomitant with approximately 50-60% inhibition of tubulin addition. Incorporation of colchicine-tubulin complex continued slowly with time, without significant additional change in the rate of tubulin addition. In contrast, addition of unliganded colchicine to microtubule suspensions resulted in incorporation of small numbers of colchicine molecules at microtubule ends and inhibition of tubulin addition only after periods of time that varied from several minutes to approximately 20 min depending upon the concentration of colchicine. Inhibition of tubulin addition beginning with unliganded colchicine increased slowly with time, concomitant with increases in the concentration of final-state tubulin-colchicine complex and the amount of colchicine bound per microtubule end. The results indicate that inhibition of tubulin incorporation at microtubule ends is caused by colchicine-liganded tubulin in the form of a final-state complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1973

The mechanism of action of colchicine. Colchicine binding properties of sea urchin sperm tail outer doublet tubulin.

The thermal depolymerization procedure of Stephens (1970. J. Mol. Biol. 47:353) has been employed for solubilization of Strongylocentrotus purpuratus sperm tail outer doublet microtubules with the use of a buffer during solubilization which is of optimal pH and ionic strength for the preservation of colchicine binding activity of chick embryo brain tubulin. Colchicine binding values were corrected for first-order decay during heat solubilization at 50 degrees C (t((1/2)) = 5.4 min) and incubation with colchicine at 37 degrees C in the presence of vinblastine sulfate (t((1/2)) = 485 min). The colchicine binding properties of heat-solubilized outer doublet tubulin were qualitatively identical with those of other soluble forms of tubulin. The solubilized tubulin (mol wt, 115,000) bound 0.9 +/- 0.2 mol of colchicine per mol of tubulin, with a binding constant of 6.3 x 10(5) liters/mol at 37 degrees C. The colchicine binding reaction was both time and temperature dependent, and the binding of colchicine was prevented in a competitive manner by podophyllotoxin (K(i) = 1.3 x 10(-6) M). The first-order decay of colchicine binding activity was substantially decreased by the addition of the vinca alkaloids, vinblastine sulfate or vincristine sulfate, thus demonstrating the presence of a vinca alkaloid binding site(s) on the outer doublet tubulin. Tubulin contained within the assembled microtubules did not decay. Intact outer doublet microtubules bound less than 0.001 mol of colchicine per mol of tubulin contained in the microtubules, under conditions where soluble tubulin would have bound 1 mol of colchicine per mol of tubulin (saturating concentration of colchicine, no decay of colchicine binding activity). The presence of colchicine had no effect on the rate of solubilization of outer doublet microtubules during incubation at 37 degrees C. Therefore, the colchicine binding site on tubulin is blocked (not available to bind colchicine) when the tubulin is in the assembled outer doublet microtubules.

Animals↗
PubMed1992

Colchicine-specific Fab fragments alter colchicine disposition in rabbits.

High-affinity goat antibodies and Fab fragments (Ka = 1.1 x 10(10) M(-1) specific to colchicine were prepared to study their effect on colchicine pharmacokinetics in rabbits. First, colchicine disposition kinetics were investigated in four control rabbits after administration of 0.1 mg/kg i.v. Total and free plasma and urine colchicine were assayed by specific radioimmunoassay. The mean elimination half-life of total plasma colchicine was 16 +/- 2.9 h. Colchicine has a large volume of distribution (8.8 +/- 1.8 l/kg) and a low systemic clearance (114.6 +/- 3.4 ml.h-1.kg-1). Renal clearance represented 30.7 +/- 1.9% of total body clearance. The free plasma colchicine fraction was 70% after equilibrium dialysis. Second, 1.5 h after injection of 0.1 mg/kg colchicine, four rabbits were infused over 0.25 h with colchicine-specific Fab fragments at a half-stoichiometrically equivalent dose compared to the colchicine dose. Within 15 min after Fab infusion, total colchicine concentrations increased 10- to 16-fold. Mean area under the plasma concentration-time curves increased 20-fold compared to controls. The free plasma fraction decreased to an undetectable level over a period of 2 h. The Fab fragment administration also produced, respectively, a 24- and 17-fold decrease in the volume of distribution and systemic clearance. Colchicine recovered in urine was significantly higher than in the control group: 44.7 +/- 2.3 and 30.9 +/- 2% of the dose, respectively (P less than .05). These data suggest that high-affinity colchicine-specific Fab fragments can sequestrate and extract colchicine from tissues to the vascular compartment with subsequent colchicine excretion by the renal route.

Animals↗
PubMed2006

Is P-glycoprotein (ABCB1) a phase 0 or a phase 3 colchicine transporter depending on colchicine exposure conditions?

This study investigates the P-glycoprotein (Pgp)-mediated transport of its substrates in accumulation or efflux modes under steady-state conditions. The kinetics of colchicine uptake and efflux, a substrate of both Pgp and intracellular tubulin, were studied in HL60 and HL60/DNR cells; HL60/DNR cells contain 25 times more Pgp than do HL60 cells. HL60/DNR cells in a medium containing 6.25 nM colchicine, which mimics therapeutic conditions, reached steady-state twice as rapidly as did HL60 cells, and accumulated 24-times less colchicine than did HL60 cells. The Pgp inhibitor GF120918, increased colchicine uptake by HL60 cells 1.2-fold and that of HL60/DNR cells 17-fold, while it had no effect on colchicine efflux from either cell line that had been incubated with colchicine for 24 h. Colchicine kinetics fitted well a two closed-compartment model, showing that the low intracellular accumulation of colchicine in HL60/DNR cells resulted from a 11-fold decrease in colchicine uptake and a 2.3-fold increase in colchicine efflux, that could be attributed to Pgp-mediated efflux activity in HL60/DNR cells. Intracellular colchicine was mainly and similarly distributed in the cytosol in both cell lines. These data demonstrate that the kinetics of the intracellular colchicine accumulation depend on the density of Pgp and that Pgp is more a phase 0 (preventing cellular uptake) than a phase 3 (effluxing intracellular substrate) transporter under steady-state conditions, although the situation is reversed after a short incubation time (30 min), when intracellular free colchicine concentration is probably high enough for it to be removed from the cell by Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Effect of colchicine-specific Fab fragments on the hepatic clearance of colchicine.

The influence of colchicine-specific Fab fragments on hepatic metabolism and biliary excretion of colchicine was studied in the isolated perfused rat liver. Isolated rat livers were perfused for 180 min with either [3H]colchicine (initial concentration: 50 ng/ml) or Fab-[3H] colchicine in a stoichiometrical proportion at a constant flow of 100 ml/min in a recirculating system. Based on perfusate concentrations, the hepatic extraction ratio of colchicine was more than 15-fold decreased when colchicine was bound to Fab fragments (E = 0.011 +/- 0.001) than when it was infused alone (E = 0.16 +/- 0.01) (p < 0.01). The extensive binding of colchicine to Fab over the experimental period as demonstrated by equilibrium dialysis (97 +/- 2%) prevented hepatic uptake. At the end of the colchicine perfusion experiment, 74.2 +/- 4.9% of the radioactivity infused was excreted by the biliary route. In contrast, biliary excretion of radioactivity was 10-fold lower when [3H]colchicine was perfused complexed with Fab fragments (p < 0.01). However, the metabolic profile of colchicine was not affected by Fab fragments. The apparent half-life of colchicine metabolites calculated from biliary data was similar to that of colchicine, indicating that the biliary excretion of these metabolites was formation rate-limited. Inhibition of colchicine uptake by specific Fab fragment was confirmed in vitro with isolated hepatocytes.

Animals↗
PubMed1995

Local delivery of biodegradable microparticles containing colchicine or a colchicine analogue: effects on restenosis and implications for catheter-based drug delivery.

OBJECTIVES: This study sought to evaluate the delivery efficiency, intramural retention and antirestenotic efficacy of soluble colchicine or colchicine analogue delivered into the arterial wall after angioplasty as well as the efficacy of these medications after prolonged local release from biodegradable microparticles. BACKGROUND: Local delivery of pharmacologic agents is a potential treatment for restenosis. However, the delivery efficiency of the technique and the choice of agent to modulate cellular proliferation are unknown. It was hypothesized that restenosis would be unaffected by colchicine or a hydrophobic colchicine analogue with short intramural retention, whereas it would be reduced after prolonged local release. METHODS: Rabbit atherosclerotic femoral arteries underwent angioplasty followed by local delivery. Delivery efficiency and intramural retention of 3H-colchicine were evaluated. The effect of agents in soluble formulation or released from microparticles on angiographic and morphometric restenosis was evaluated at 2 weeks and compared with that in the control groups (angioplasty only and local infusion of carrier solution). RESULTS: Delivery of efficiency was 0.01% and intramural retention < 24 h. Neither soluble colchicine formulation reduced restenosis. Microparticles releasing the colchicine analogue reduced restenosis compared with control and colchicine microparticles but not angioplasty alone (p = 0.002). Delivery outside the artery was observed, and the long-term release of both colchicine resulted in toxicity to the adjacent musculature. CONCLUSIONS: Colchicine or the colchicine analogue did not reduce restenosis, although the long-term local release of the colchicine analogue reduced neointimal proliferation resulting from local delivery. Local delivery of cytotoxic agents with insufficient vascular specificity may be limited by toxicity to adjacent tissues resulting from a larger than expected delivery area and prolonged agent retention.

Animals↗
PubMed1989

The effect of colchicine-specific active immunization on colchicine toxicity and disposition in the rabbit.

Anti-colchicine antibodies raised in rabbits are effective at protecting rabbits from acute colchicine intoxication. The positive effect depends on the ratio between the binding site capacity of the specific antibodies and the colchicine dose. Immunized rabbits receiving 6 mg/kg colchicine intravenously (LD100) died within 8 h as rapidly as those of the non-immunized control group. In contrast, if the colchicine dose was reduced to 3 mg/kg (LD83), rabbits were protected and mortality decreased to 17%. Study of plasma colchicine pharmacokinetics indicated that colchicine was totally sequestrated by antibodies in the 3 mg/kg group and only 55-80% sequestrated in 6 mg/kg group. This sequestration contributed to reducing colchicine diffusion into tissues (the volume of distribution decreased 7-fold) and to increasing the terminal half-life and the total body clearance of the drug. Moreover, as the slope of the dose-lethality curve was steep, a small binding capacity was sufficient to neutralize colchicine toxicity at 3 mg/kg. Results clearly indicate that anti-colchicine antibodies are able to effectively sequestrate colchicine. Moreover, the amount of circulating antibodies is a crucial limiting factor for the effectiveness of immunotoxicotherapy.

Animals↗
PubMed1997

Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation.

Colchicine disposition involves both active biliary and renal excretion of parent drug, and at least in mammals a substantial fraction undergoes hepatic demethylation prior to excretion. We investigated the biotransformation of [3H]colchicine in a panel of microsomal preparations obtained from sixteen human liver samples. The production rate of the main metabolites of colchicine's 3-demethylcolchicine (3DMC) and 2-demethylcolchicine (2DMC), was linear in relation to incubation time, cytochrome (P450) content, and substrate concentration. Following the incubation of colchicine (5 nM) with microsomes in the presence of an NADPH-generating system for 60 min, 9.8% and 5.5% of the substrate were metabolized to 3DMC and 2DMC, respectively. The formation rate of colchicine metabolites exhibited a marked variation between the different microsomal preparations. The formation rates of both colchicine metabolites were correlated significantly with nifedipine oxidase activity, a marker of CYP3A4 activity (r = 0.96, P < 0.001), but not with the metabolic markers of CYP2A6, CYP2C19, CYP2C9, CYP2D6, and CYP2E1 activities. Chemical inhibition of CYP3A4 by preincubation with gestodene (40 microM) or troleandomycin (40 microM) reduced the formation of 3DMC and 2DMC by 70 and 80%, respectively, whereas quinidine, diethyldithiocarbamate, and sulfaphenazole had no inhibitory effect. Similarly, antibodies raised against CYP3A4 almost completely abolished colchicine demethylation and nifedipine oxidase activity, but preimmune IgG had no effect. In conclusion, colchicine was metabolized to 3DMC and 2DMC by human liver microsomes. The production of colchicine metabolites was mediated by CYP3A4, and its rate varied greatly between microsomal preparations obtained from different liver samples. The coadministration of colchicine with known inhibitors or substrates of CYP3A4 may inhibit colchicine metabolism, resulting in concentration-related toxicity.

Colchicine↗
PubMed2001

P-glycoprotein-mediated colchicine resistance in different cell lines correlates with the effects of colchicine on P-glycoprotein conformation.

The multidrug transporter P-glycoprotein (Pgp) is an ATPase efflux pump for multiple cytotoxic agents, including vinblastine and colchicine. We have found that resistance to vinblastine but not to colchicine in cell lines derived from different types of tissues and expressing the wild-type human Pgp correlates with the Pgp density. Vinblastine induces a conformational change in Pgp, evidenced by increased reactivity with a conformation-sensitive monoclonal antibody UIC2, in all the tested cell lines. In contrast, colchicine increases the UIC2 reactivity in only some of the cell lines. In those lines where colchicine alone did not affect UIC2 reactivity, this drug was, however, able to reverse the vinblastine-induced increase in UIC2 reactivity. The magnitude of the increase in UIC2 reactivity in the presence of saturating concentrations of colchicine correlates with the relative ability of Pgp to confer colchicine resistance in different cell lines, suggesting the existence of some cell-specific factors that have a coordinate effect on the ability of colchicine to induce conformational transitions and to be transported by Pgp. Colchicine, like vinblastine, reverses the decrease in UIC2 reactivity produced by nonhydrolyzable nucleotides, but unlike vinblastine, it does not reverse the effect of ATP at a high concentration. Colchicine, however, decreases the Hill number for the effect of ATP on the UIC2 reactivity from 2 to 1. Colchicine increases the UIC2 reactivity and reverses the effect of ATP in ATPase-deficient Pgp mutants, but not in the wild-type Pgp expressed in the same cellular background, suggesting that ATP hydrolysis counteracts the effects of colchicine on the Pgp conformation.

3T3 Cells↗
PubMed1989

Influence of goat colchicine specific antibodies on murine colchicine disposition.

The potential use of colchicine-specific antibodies (IgG(C)) to overcome colchicine intoxication in mice is of interest in human poisoning. Pharmacokinetics in mice are similar to those in humans. A short distribution half-life (t 1/2 a = 34 min) is associated with a long elimination half-life (t1/2 beta = 48 h) together with a large volume of distribution at steady-state (Vss = 2.5 l/kg) and a low total body clearance (ClT = 1 ml/min/kg). This extensive and rapid distribution to tissues impairs the success of conventional therapies. Despite the administration of a relatively low amount of IgG (C) (15% binding sites vs, colchicine molecules), the beneficial effect of IgG(C) is demonstrated by the alteration in colchicine pharmacokinetics which occurs rapidly following IgG(C) administration as demonstrated by rise in blood toxin concentrations (4-fold relative to IgG(N)-treated controls). This sequestration in the blood is associated with a colchicine redistribution from peripheral to the blood compartment. This extraction effect is revealed by lower colchicine tissue levels in IgG(C)-treated mice than in controls. As a consequence, Vss decreased in the IgG(C) group. Moreover, ClT is diminished in the IgG(C)-treated group because the relatively large immunoglobulin can not be excreted renally. In addition to this toxin displacement, study of free and bound colchicine plasma levels shows a lower percentage of free toxin in the IgG(C)-treated group (33 to 0%) compared to 70% in the control group. This pharmacokinetic study provides evidence that the administration of IgG(C) alters the colchicine disposition by sequestrating and extracting colchicine in blood compartment.

Animals↗
PubMed1991

Dose-dependent reversal of acute murine colchicine poisoning by goat colchicine-specific Fab fragments.

The use of colchicine-specific Fab fragments is of interest in human poisoning. In the present study, we show the efficacy of Fab fragments in reversing colchicine toxicity in mice. High affinity antibodies (Ka = 2 x 10(10) M-1) against colchicine were raised in goats; Fab fragments were purified by DEAE chromatography after papain hydrolysis of IgG. Mice were intoxicated with a 100% lethal colchicine dose (3.8 mg/kg). When a half molar dose (M/2) of Fab fragments in relation to the colchicine dose was intravenously and intraperitoneally administered 90 min after colchicine infusion using a multiple dosage schedule, 80% of the Fab-treated mice survived compared to the control group which did not receive Fab fragments (P less than 0.01). Using a M/4 and M/8 dose of Fab fragments, the mortality was respectively 50% and 80%. The dose-effect relationship was linear (r = 0.99). Delayed administration of a M/2 dose of Fab fragments 6 h after colchicine administration resulted in 50% survival (P less than 0.01). Body temperature and body weight were selective markers of the severity of the intoxication. In the control group, a marked decrease of body temperature was observed following the first few hours after the intoxication (-21% compared to basal value 48 h after colchicine). In the Fab-treated group, the decrease was inversely related to the Fab fragment dose. Body temperature returned to the basal values 7 days after intoxication. A progressive decrease in body weight was concomitantly observed in intoxicated mice until death, while values returned to baseline 9 days after colchicine in surviving Fab-treated mice.

Animals↗
PubMed1991

Reversal of murine colchicine toxicity by colchicine-specific Fab fragments.

High-affinity Fab fragments (2 x 10(10) M-1) specific to colchicine were produced to evaluate their potency in reversing murine colchicine intoxication. Intraperitoneal injection of a 4.46 mg/kg colchicine dose was lethal for 100% of mice. 1.5 h after colchicine administration, a group of 10 mice was treated with colchicine-specific Fab fragments at a half-stoichiometrical dose compared to the colchicine dose by intravenous and intraperitoneal routes. 70% of the Fab-infused mice survived (P less than 0.01). This high efficiency of colchicine-specific Fab fragments in reversing acute murine colchicine toxicity suggests that Fab fragments would be an efficient antidote for the treatment of human colchicine poisoning.

Animals↗
PubMed1990

Reversal of colchicine-induced mitotic arrest in Chinese hamster cells with a colchicine-specific monoclonal antibody.

The ability of a high-affinity colchicine-binding monoclonal antibody to reverse the effects of colchicine on Chinese hamster ovary cells was investigated. Using flow cytometry, a complete mitotic blockade was demonstrated after 16 hours with 2.5 x 10(-7) mol/l (molar) colchicine. Colchicine-induced changes were reversible when equimolar antibody was added simultaneously with or up to 6 hours after colchicine. With further delay in addition of antibody, a progressive irreversible increase in mitotic blockade and increase in mean cell size was observed. Prolonged colchicine exposure, without antibody reversal, led to polyploidy and structural chromosome breakage. Early antibody reversal restored cells to the diploid state, whereas delayed reversal resulted in a time-dependent increase in polyploidy. Colchicine-induced polyploidy and chromosomal aberrations may be the basis for both colchicine toxicity and the time-dependent increase in irreversibility of colchicine effects.

Animals↗
PubMed1995

Efflux of intracellular colchicine in lymphocytes with colchicine-specific Fab fragments.

Uptake of [3H]colchicine (2.5 ng/ml) by human lymphocytes in culture was slow in the length of time to reach steady state (> 48 hr) and was limited in the maximal intracellular colchicine amount (1-2% of total extracellular colchicine). Efflux of intracellular colchicine was investigated 40 hr after colchicine cell exposure by using either washing of the extracellular medium or adding different colchicine-specific Fab fragments:colchicine dose molar ratios of 0.5, 1 and 5. Except for the 0.5 dose molar ratio, the kinetics of [3H]colchicine efflux from lymphocytes induced by extracellular specific Fab fragments were similar to those obtained by washing and were characterized by a first-order decline with half-lives ranging from 15.5 to 16.4 hr. These half-lives were in the same range as those characterizing the dissociation of colchicine from the intracellular tubulin receptor. Our data demonstrate that a tightly bound intracellular toxin may be extracted by antibody with high affinity for the toxin present in the extracellular space at a rate depending on the rate of dissociation of the toxin from its receptor.

Biological Transport↗
PubMed1965

THE MECHANISM OF COLCHICINE INHIBITION OF MITOSIS. I. KINETICS OF INHIBITION AND THE BINDING OF H3-COLCHICINE.

H(3)-colchicine of high specific activity (2.5 curies per mM) was prepared in order to study the mechanism of colchicine inhibition of mitosis in cultures of human cells, strain K.B. No direct effects on the duration of the cell cycle or macromolecular synthesis were demonstrable at a concentration of colchicine which completely inhibited mitosis. The radioactive compound was bound to the cells at a rate proportional to colchicine concentration. The binding appeared to be reversible since the radioactivity of the cells reached a maximum value for a given concentration and was slowly lost after resuspension of the cells in fresh medium. A suitable exposure to colchicine produced accumulation of metaphase-blocked mitoses after the colchicine was removed from the medium. An exposure of 6 to 8 hours at 10(-7)M was sufficient to block essentially all the cells in metaphase, thus indicating that colchicine is bound to the majority of interphase cells. The data are in quantitative agreement with a mechanism involving reversible binding of colchicine to a set of cellular sites. Based on the correlation between the time of first appearance of blocked mitoses and the radioactivity per cell, it is suggested that if a critical fraction (3 to 5 per cent) of the sites are complexed, the cell is unable to form a functional mitotic spindle.

Adenine↗
PubMed2005

Biphasic kinetics of the colchicine-tubulin interaction: role of amino acids surrounding the A ring of bound colchicine molecule.

Isotypes of vertebrate tubulin have variable amino acid sequences, which are clustered at their C-terminal ends. Isotypes bind colchicine at different on-rates and affinity constants. The kinetics of colchicine binding to purified (unfractionated) brain tubulin have been reported to be biphasic under pseudo-first-order conditions. Experiments with individual isotypes established that the presence of beta(III) in the purified tubulin is responsible for the biphasic kinetics. Because the isotypes mainly differ at the C termini, the colchicine-binding kinetics of unfractionated tubulin and the beta(III) isotype, cleaved at the C termini, have been tested under pseudo-first-order conditions. Removal of the C termini made no difference to the nature of the kinetics. Sequence alignment of different beta isotypes of tubulin showed that besides the C-terminal region, there are differences in the main body as well. To establish whether these differences lie at the colchicine-binding site or not, homology modeling of all beta-tubulin isotypes was done. We found that the isotypes differed from each other in the amino acids located near the A ring of colchicine at the colchicine-binding site on beta tubulin. While the beta(III) isotype has two hydrophilic residues (serine(242) and threonine(317)), both beta(II) and beta(IV) have two hydrophobic residues (leucine(242) and alanine(317)). beta(II) has isoleucine at position 318, while beta(III) and beta(IV) have valine at that position. Thus, these alterations in the nature of the amino acids surrounding the colchicine site could be responsible for the different colchicine-binding kinetics of the different isotypes of tubulin.

Alanine↗
PubMed2003

Intravenous colchicine for treatment of patients with familial Mediterranean fever unresponsive to oral colchicine.

OBJECTIVE: To evaluate the efficacy and safety of weekly intravenous (IV) colchicine, in addition to oral colchicine therapy, in a subset of patients with familial Mediterranean fever (FMF) unresponsive to oral colchicine prophylaxis. METHODS: Thirteen patients with frequent FMF attacks, despite oral doses of 2-3 mg/day colchicine, were treated with weekly IV injections of 1 mg colchicine for 12 weeks in an open-label pilot study. Patients were evaluated periodically for the number and severity of their attacks, use of analgesics, and erythrocyte sedimentation rate (ESR). RESULTS: A 50% reduction in attack frequency and attack severity in at least one site was achieved by 10 and 6 of the 13 study patients, respectively (p < 0.001 and p < 0.01). Mean number of abdominal attacks declined significantly from 4.2 +/- 3.0 per patient at baseline to 1.9 +/- 2.6 attacks at the end of the third month of the study (p = 0.0002). The mean severity of abdominal attacks declined from a baseline of 6.1 +/- 0.95 to 3.9 +/- 2.8 after 3 months (p = 0.02). Comparable significant change was observed in chest attacks, ESR, and number of analgesic tablets used. Joint attacks were unrelieved during the study period. The treatment was safe and well tolerated, without side effects. CONCLUSION: Treatment with weekly IV colchicine injections in addition to oral colchicine therapy is effective and safe in patients with FMF refractory to oral colchicine.

Administration, Oral↗