Tìm theo
Rofecoxib
Thuốc giảm đau, hạ sốt, chống viêm không steroid, điều trị Gút và các bệnh xương khớp
Thuốc Gốc
Small Molecule
CAS: 162011-90-7
ATC: M01AH02
ĐG : AQ Pharmaceuticals Inc. , http://www.aqpharmaceuticals.com
CTHH: C17H14O4S
PTK: 314.356
Rofecoxib is used for the treatment of osteoarthritis, rheumatoid arthritis, acute pain in adults, and primary dysmenorrhea, as well as acute treatment of migraine attacks with or without auras. Rofecoxib is a solid. This compound belongs to the stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids. Rofecoxib has a half-life of 17 hours and its mean oral bioavailability at therapeutically recommended doses of 125, 25, and 50 mg is approximately 93%. The proteins that rofecoxib target include elastin and prostaglandin G/H synthase 2. Cytochrome P450 1A2, Cytochrome P450 3A4, Cytochrome P450 2C9, Cytochrome P450 2C8, and Prostaglandin G/H synthase 1 are known to metabolize rofecoxib. On September 30, 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C17H14O4S
Phân tử khối
314.356
Monoisotopic mass
314.061279626
InChI
InChI=1S/C17H14O4S/c1-22(19,20)14-9-7-12(8-10-14)15-11-21-17(18)16(15)13-5-3-2-4-6-13/h2-10H,11H2,1H3
InChI Key
InChIKey=RZJQGNCSTQAWON-UHFFFAOYSA-N
IUPAC Name
4-(4-methanesulfonylphenyl)-3-phenyl-2,5-dihydrofuran-2-one
Traditional IUPAC Name
rofecoxib
SMILES
CS(=O)(=O)C1=CC=C(C=C1)C1=C(C(=O)OC1)C1=CC=CC=C1
Độ hòa tan
Insoluble
logP
3.2
logS
-4.5
pKa (strongest acidic)
14.84
pKa (Strongest Basic)
-7
PSA
60.44 Å2
Refractivity
84.08 m3·mol-1
Polarizability
31.74 Å3
Rotatable Bond Count
3
H Bond Acceptor Count
3
H Bond Donor Count
0
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Unlike celecoxib, rofecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. Like other NSAIDs, rofecoxib exhibits anti-inflammatory, analgesic, and antipyretic activity. NSAIDs appear to inhibit prostaglandin synthesis via the inhibition of cyclooxygenase (COX), which are responsible for catalyzing the formation of prostaglandins in the arachidonic acid pathyway. There are at least two isoenzymes, COX-1 and COX-2, that have been identified. Although the exact mechanisms have not been clearly established, NSAIDs exert their anti-inflammatory, analgesic, and antipyretic primarily through the inhibition of COX-2. The inhibition of COX-1 is principally responsible for the negative effects on the GI mucosa. As rofecoxib is selective for COX-2, it may be potentially associated with a decreased risk of certain adverse events, but more data is needed to fully evaulate the drug.
Cơ Chế Tác Dụng : Rofecoxib is used for the treatment of osteoarthritis, rheumatoid arthritis, acute pain in adults, and primary dysmenorrhea, as well as acute treatment of migraine attacks with or without auras. Rofecoxib is a solid. This compound belongs to the stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids. Rofecoxib has a half-life of 17 hours and its mean oral bioavailability at therapeutically recommended doses of 125, 25, and 50 mg is approximately 93%. The proteins that rofecoxib target include elastin and prostaglandin G/H synthase 2. Cytochrome P450 1A2, Cytochrome P450 3A4, Cytochrome P450 2C9, Cytochrome P450 2C8, and Prostaglandin G/H synthase 1 are known to metabolize rofecoxib. On September 30, 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use. The anti-inflammatory, analgesic, and antipyretic effects of NSAIDs appear to result from the inhibition of prostaglandin synthesis. Although the exact mechanism of action has not been determined, these effects appear to be mediated through the inhibition of the COX-2 isoenzyme at the sites of inflammation with subsequent reduction in the synthesis of certain prostaglandins from their arachidonic acid precursors. Rofecoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, which is important for the mediation of inflammation and pain. Unlike non-selective NSAIDs, rofecoxib does not inhibit platelet aggregation. It also has little to no affinity for COX-1.
Dược Động Học :
▧ Absorption :
The mean oral bioavailability of rofecoxib at therapeutically recommended doses of 12.5, 25, and 50 mg is approximately 93%.
▧ Protein binding :
87%
▧ Metabolism :
Hepatic. Metabolism of rofecoxib is primarily mediated through reduction by cytosolic enzymes. The principal metabolic products are the cis-dihydro and trans-dihydro derivatives of rofecoxib, which account for nearly 56% of recovered radioactivity in the urine. An additional 8.8% of the dose was recovered as the glucuronide of the hydroxy derivative, a product of oxidative metabolism. The biotransformation of rofecoxib and this metabolite is reversible in humans to a limited extent (< 5%). These metabolites are inactive as COX-1 or COX-2 inhibitors. Cytochrome P450 plays a minor role in metabolism of rofecoxib.
▧ Half Life :
17 hours
Độc Tính : No overdoses of rofecoxib were reported during clinical trials. Administration of single doses of rofecoxib 1000 mg to 6 healthy volunteers and multiple doses of 250 mg/day for 14 days to 75 healthy volunteers did not result in serious toxicity.
Chỉ Định : For the treatment of osteoarthritis, rheumatoid arthritis, acute pain in adults, and primary dysmenorrhea, as well as acute treatment of migraine attacks with or without auras.
Tương Tác Thuốc :
  • Aminophylline Rofecoxib increases the effect and toxicity of theophylline
  • Lithium The COX-2 inhibitor increases serum levels of lithium
  • Methotrexate Rofecoxib increases the levels of methotrexate
  • Oxtriphylline Rofecoxib increases the effect and toxicity of theophylline
  • Theophylline Rofecoxib increases the effect and toxicity of theophylline
Liều Lượng & Cách Dùng : Suspension - Oral
Tablet - Oral
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Vioxx
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00533
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5090
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504787
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07590
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00568
ChemSpider
http://www.chemspider.com/Chemical-Structure.4911.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=22369
PharmGKB
http://www.pharmgkb.org/drug/PA451268
Wikipedia
http://en.wikipedia.org/wiki/Rofecoxib
RxList
http://www.rxlist.com/cgi/generic/rofecox.htm
Drugs.com
http://www.drugs.com/mtm/rofecoxib.html
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