Colchicina Seid Tác dụng

Pharmacotherapeutic group: M04AX Other antigout preparations.
Pharmacology: Pharmacodynamics: Colchicine is used to relieve acute gout attacks and for the prophylaxis of acute attacks. Colchicine is also indicated for the treatment of chronic gout and familial Mediterranean fever.
The mechanism of action of colchicine is not fully understood. Colchicine probably produces an immediate response in gout attacks due to a reduction in the inflammatory reaction caused by urate crystals. This effect occurs due to different actions, including a reduction in leukocyte mobility.
Colchicine inhibits the phagocytosis of urate microcrystals, thereby reducing the production of lactic acid and maintaining a normal local pH. Acidity enhances the precipitation of urate crystals, which is the cause of gout attacks.
Colchicine has no analgesic activity and has no effect on the plasma concentrations or clearance of uric acid. It also shows antimitotic activity (inhibition or prevention of cell division in the meta- and anaphases).
Colchicine presents other pharmacological activities in animals, where it impairs neuromuscular function, enhances gastrointestinal activity by neurogenic stimulation, increases the sensitivity to central depressants, enhances the response to sympathomimetics, depresses the respiratory centre, causes vasoconstriction, causes hypertension by vasomotor centre stimulation and decreases body temperature.
The multicentre, double-blind, placebo-controlled AGREE (Acute Gout Flare Receiving Colchicine Evaluation) study, evaluated the percentage of patients who responded to the following colchicine treatment regimes: Group 1: High dose of colchicine (1.2 mg followed by 0.6 mg/hour for 6 hours [total dose: 4.8 mg]).
Group 2: Low dose of colchicine (1.2 mg followed by 0.6 mg/hour for 1 hour [1.8 mg]).
Group 3: Placebo.
A total of 184 patients were included in the intention to treat analysis. The primary endpoint of this study was the percentage of treatment responders, defined as any patient who presented a ≥50% reduction in perceived pain within 24 hours of the first dose of drug with no rescue drugs. A total of 28 of 74 patients in the low-dose group (37.8%), 17 of 52 patients in the high-dose group (32.7%) and 9 of 58 patients in the placebo group (15.5%) responded to treatment (p=0.005 and p=0.034, respectively, versus placebo). During the first few hours of treatment, 23 (31.1%) patients in the low-dose group (p=0.027 versus placebo), 18 (34.6%) patients in the high-dose group (p=0.103 versus placebo) and 29 (50%) patients in the placebo group required rescue drugs. The low-dose group showed a similar adverse effects profile to the placebo group, with an odds ratio (OR) of 1.5 (95% confidence interval [95% CI] 0.7-3.2). A high dose of colchicine was significantly associated with diarrhoea, vomiting and other adverse events in comparison with the use of a low dose of colchicine or placebo.
Forty patients in the high-dose group (76.9%) experienced diarrhoea (OR: 21.3; 95% CI 7.9-56.9), 10 (19.2%) experienced severe diarrhoea and a further nine (17.3%) vomiting. In the low-dose group, 23% of patients experienced diarrhoea (OR: 1.9; 95% CI 0.8-4.8) and none experienced either severe diarrhoea or vomiting.
Low doses of colchicine gave similar peak plasma concentration and efficacy values to high doses for the treatment of acute gout attacks, with a similar safety profile to placebo.
Pharmacokinetics: Colchicine is absorbed orally with an approximate bioavailability of 45%.
Approximately 39% is bound to albumin, with no direct relationship with concentration.
It binds to all tissues, mainly the intestinal mucosa, the liver, kidney and spleen, but not to the myocardium, skeletal muscle or lungs.
It has been reported that colchicine crosses the placenta, with foetal plasma levels of approximately 15% of those found in the mother. The concentration in human breast milk is similar to that observed in plasma from the mother.
The mean volume of distribution ranges from 2 to 8 l/kg.
Colchicine is partially metabolised in the liver by demethylation to two main metabolites, namely 2-O-demethylcolchicine and 3-O-demethylcolchicine, and a minor metabolite, namely 10-O-demethylcolchicine. CYP3A4 is involved in colchicine metabolism. The plasma levels of the two main metabolites are less than 5% of that for colchicine. The pharmacological activity of these metabolites is unknown.
Colchicine and its metabolites undergo enterohepatic circulation.
Clearance is significantly decreased and the half-life extended in patients with severe hepatic impairment. The findings in patients with mild to moderate hepatic impairment show high interpatient variability.
Renal clearance of colchicine has been estimated at 0.727 l/h/kg in patients with good renal function. Renal clearance was reduced by 75% in patients with severe renal impairment. There are no data in patients with mild to moderate renal impairment.
Colchicine is not cleared by haemodialysis.
The elimination half-life in healthy volunteers (aged between 25 and 28 years) reported in the literature ranges from 26.6 to 31.2 hours.
Colchicine is a substrate of P glycoprotein.
No gender-based pharmacokinetic differences have been reported.
The pharmacokinetics in paediatric patients have not been described.
According to a study published in elderly patients, the mean peak plasma concentration and AUC were twice as high as those in young subjects. This difference could be explained by reduced renal function in the former.
Toxicology: Preclinical safety data: Preclinical safety data showed no risks in humans other than those expected due to the established administration conditions. However, colchicine was teratogenic in animals.