Tìm theo
Colchicine
Các tên gọi khác (5 ) :
  • Colchicin
  • Colchicina
  • Colchicinum
  • SID26747941
  • SID49671357
Thuốc giảm đau, hạ sốt, chống viêm không steroid, điều trị Gút và các bệnh xương khớp
Thuốc Gốc
Small Molecule
CAS: 64-86-8
ATC: M04AC01
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C22H25NO6
PTK: 399.437
A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C22H25NO6
Phân tử khối
399.437
Monoisotopic mass
399.168187537
InChI
InChI=1S/C22H25NO6/c1-12(24)23-16-8-6-13-10-19(27-3)21(28-4)22(29-5)20(13)14-7-9-18(26-2)17(25)11-15(14)16/h7,9-11,16H,6,8H2,1-5H3,(H,23,24)
InChI Key
InChIKey=IAKHMKGGTNLKSZ-UHFFFAOYSA-N
IUPAC Name
N-{3,4,5,14-tetramethoxy-13-oxotricyclo[9.5.0.0^{2,7}]hexadeca-1(16),2(7),3,5,11,14-hexaen-10-yl}acetamide
Traditional IUPAC Name
colchicine
SMILES
COC1=CC2=C(C(OC)=C1OC)C1=CC=C(OC)C(=O)C=C1C(CC2)NC(C)=O
Độ tan chảy
156 °C
Độ hòa tan
4.5E+004 mg/L (at 25 °C)
logP
1.30
logS
-4.2
pKa (strongest acidic)
15.06
pKa (Strongest Basic)
-0.038
PSA
83.09 Å2
Refractivity
111.38 m3·mol-1
Polarizability
42.41 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
6
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
pKa
1.85
Dược Lực Học : Colchicine is a highly poisonous alkaloid, originally extracted from plants of the genus Colchicum (Autumn crocus, also known as the "Meadow saffron"). Originally used to treat rheumatic complaints and especially gout, it was also prescribed for its cathartic and emetic effects. Its present medicinal use is mainly in the treatment of gout; as well, it is being investigated for its potential use as an anti-cancer drug. It can also be used as initial treatment for pericarditis and preventing recurrences of the condition.
Cơ Chế Tác Dụng : A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [PubChem] The precise mechanism of action has not been completely established. In patients with gout, colchicine apparently interrupts the cycle of monosodium urate crystal deposition in joint tissues and the resultant inflammatory response that initiates and sustains an acute attack. Colchicine decreases leukocyte chemotaxis and phagocytosis and inhibits the formation and release of a chemotactic glycoprotein that is produced during phagocytosis of urate crystals. Colchicine also inhibits urate crystal deposition, which is enhanced by a low pH in the tissues, probably by inhibiting oxidation of glucose and subsequent lactic acid production in leukocytes. Colchicine has no analgesic or antihyperuricemic activity. Colchicine inhibits microtubule assembly in various cells, including leukocytes, probably by binding to and interfering with polymerization of the microtubule subunit tubulin. Although some studies have found that this action probably does not contribute significantly to colchicine's antigout action, a recent in vitro study has shown that it may be at least partially involved.
Dược Động Học :
▧ Absorption :
Colchicine is rapidly absorbed after oral administration, probably from the jejunum and ileum. However, the rate and extent of absorption are variable, depending on the tablet dissolution rate; variability in gastric emptying, intestinal motility, and pH at the absorption site; and the extent to which colchicine is bound to microtubules in gastrointestinal mucosal cells.
▧ Volume of Distribution :
* 5 to 8 L/kg [healthy young volunteers]
▧ Protein binding :
Low to moderate (30 to 50%).
▧ Metabolism :
Probably hepatic. Although colchicine metabolites have not been identified in humans, metabolism by mammalian hepatic microsomes has been demonstrated in vitro.
▧ Route of Elimination :
In healthy volunteers (n=12) 40 – 65% of 1 mg orally administered colchicine was recovered unchanged in urine. Enterohepatic recirculation and biliary excretion are also postulated to play a role in colchicine elimination.
▧ Half Life :
Elimination half-life is approximately 1 hour in healthy subjects, although a study with an extended sampling time reported mean terminal elimination half-life values of approximately 9 to 10.5 hours. Other studies have reported half-life values of approximately 2 hours in patients with alcoholic cirrhosis and approximately 2.5 hours in patients with familial Mediterranean fever.
▧ Clearance :
* 0.17 L/hr/kg [familial Mediterranean fever patients with end-stage renal disease] * 0.73 L/hr/kg [familial Mediterranean fever patients with normal renal function]
Độc Tính : The onset of toxic effects is usually delayed for several hours or more after the ingestion of an acute overdose. Nausea, vomiting, abdominal pain, and diarrhea occur first. The diarrhea may be bloody due to hemorrhagic gastroenteritis. Burning sensations of the throat, stomach, and skin may be prominent symptoms. Extensive vascular damage may result in shock. Kidney damage, evidenced by hematuria and oliguria, may occur. Muscular weakness may be marked, and ascending paralysis of the central nervous system may develop; the patient usually remains conscious. Delirium and convulsions may occur. Death due to respiratory arrest may result. Although death from the ingestion of as little as 7 mg has been reported, much larger doses have been survived .
Chỉ Định : For treatment and relief of pain in attacks of acute gouty arthritis.
Tương Tác Thuốc :
  • Atorvastatin Increased risk of rhadbomyolysis with this combination.
  • Bicalutamide CYP3A4 Inhibitors like bicalutamide may increase the serum concentration of colchicine. Increase monitoring for colchicine-related toxicity when using such combinations. Use extra caution in patients with impaired renal and/or hepatic function.
  • Cerivastatin Increased risk of rhabdomyolysis with this combination
  • Clarithromycin Severe colchicine toxicity can occur
  • Clotrimazole CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of colchicine. Reduce colchicine dose (for gout flares: to 1.2 mg x 1 dose, with next dose no sooner than 3 days later; for Familial Mediterranean Fever: to no more than 1.2 mg/day) when using in combination with a moderate CYP3A4 inhibitor such as erythromycin or verapamil. Increase monitoring for colchicine-related toxicity when using such combinations. Use extra caution in patients with impaired renal and/or hepatic function.
  • Conivaptan CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. In patients with normal renal and hepatic function, reduce colchicine dose (for gout flares: to 0.6 mg x 1 dose, followed by 0.3 mg 1 hour later, with next dose no sooner than 3 days later; for gout flare prophylaxis: if target dose would otherwise be 0.6 mg daily, change to 0.3 mg every other day, and if target dose would otherwise be 0.6 mg twice daily, change to 0.3 mg daily; for Familial Mediterranean Fever: to no more than 0.6 mg/day) when using in combination with a strong CYP3A4 inhibitor such as clarithromycin or ritonavir. Increase monitoring for colchicine-related toxicity when using such combinations. Colchicine use is contraindicated in patients with impaired renal and/or hepatic function who are also receiving a strong CYP3A4 inhibitor.
  • Cyclosporine Increased toxicity of both drugs
  • Erythromycin Severe colchicine toxicity can occur
  • Fluvastatin Increased risk of rhabdomyolysis with this combination
  • Lovastatin Increased risk of rhabdomyolysis with this combination
  • Pitavastatin Increased incidence of myotoxicity including rhabdomyolysis during concomitant therapy. The mechanism of this interaction is unclear, it may arise from pharmacodynamic and/or pharmacokinetic interactions.
  • Pravastatin Increased risk of rhabdomyolysis with this combination
  • Rosuvastatin Increased risk of rhabdomyolysis with this combination
  • Simvastatin Increased risk of rhabdomyolysis with this combination
  • Telithromycin Telithromycin may reduce clearance of Colchicine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Colchicine if Telithromycin is initiated, discontinued or dose changed.
  • Troleandomycin Severe colchicine toxicity can occur
  • Verapamil Verapamil may increase the serum concentration of Colchicine. This likely occurs via Verapamil-mediated inhibition of CYP3A4 and p-glycoprotein-mediated transport. Monitor for changes in the therapeutic/adverse effects of Colchicine if Verapamil is initiated, discontinued or dose changed.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of colchicine by decreasing its metabolism. A dose reduction of colchicine is recommended along with increased monitoring for colchicine toxicity. Concomitant therapy is contraindicated in patients with renal and/or hepatic impairment.
Liều Lượng & Cách Dùng : Solution / drops - Oral
Solution / drops - Oral
Tablet - Oral
Tablet - Oral
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Colcrys 0.6 mg tablet
    Giá bán buôn : USD >5.82
    Đơn vị tính : tablet
  • Biệt dược thương mại : Colchicine powder
    Giá bán buôn : USD >306.6
    Đơn vị tính : g
  • Biệt dược thương mại : Colchicine 1 mg Tablet
    Giá bán buôn : USD >0.55
    Đơn vị tính : tablet
  • Biệt dược thương mại : Colchicine 0.6 mg tablet
    Giá bán buôn : USD >0.58
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Colcrys
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01394
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07592
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00570
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/13310-119-07
PharmGKB
http://www.pharmgkb.org/drug/PA449092
Wikipedia
http://en.wikipedia.org/wiki/Colchicine
RxList
http://www.rxlist.com/cgi/generic/colch.htm
Drugs.com
http://www.drugs.com/cdi/colchicine.html
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