Tìm theo
Rosiglitazone
Các tên gọi khác (6 ) :
  • (±)-5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione
  • (RS)-5-{4-[2-(Methyl-2-pyridylamino)ethoxy]benzyl}-2,4-thiazolidinedion
  • Rosiglitazon
  • Rosiglitazona
  • Rosiglitazone
  • Rosiglitazonum
Hormon, Nội tiết tố
Thuốc Gốc
Small Molecule
CAS: 122320-73-4
ATC: A10BG02
ĐG : A-S Medication Solutions LLC , http://orders.a-smeds.com
CTHH: C18H19N3O3S
PTK: 357.427
Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is marketed by the pharmaceutical company GlaxoSmithKline as a stand-alone drug (Avandia) and in combination with metformin (Avandamet) or with glimepiride (Avandaryl). Like other thiazolidinediones, the mechanism of action of rosiglitazone is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPARγ. Rosiglitazone is a selective ligand of PPARγ, and has no PPARα-binding action. Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFκB) levels fall and inhibitor (IκB) levels increase in patients on rosiglitazone. Recent research has suggested that rosiglitazone may also be of benefit to a subset of patients with Alzheimer's disease not expressing the ApoE4 allele. This is the subject of a clinical trial currently underway.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C18H19N3O3S
Phân tử khối
357.427
Monoisotopic mass
357.114712179
InChI
InChI=1/C18H19N3O3S/c1-21(16-4-2-3-9-19-16)10-11-24-14-7-5-13(6-8-14)12-15-17(22)20-18(23)25-15/h2-9,15H,10-12H2,1H3,(H,20,22,23)
InChI Key
InChIKey=YASAKCUCGLMORW-UHFFFAOYNA-N
IUPAC Name
5-[(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione
Traditional IUPAC Name
rosiglitazone
SMILES
CN(CCOC1=CC=C(CC2SC(=O)NC2=O)C=C1)C1=CC=CC=N1
Độ tan chảy
122-123 °C
Độ hòa tan
3.80e-02 g/l
logP
2.4
logS
-4
pKa (strongest acidic)
6.84
pKa (Strongest Basic)
6.23
PSA
71.53 Å2
Refractivity
97.79 m3·mol-1
Polarizability
37.8 Å3
Rotatable Bond Count
7
H Bond Acceptor Count
5
H Bond Donor Count
1
Physiological Charge
-1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : When rosiglitazone is used as monotherapy, it is associated with increases in total cholesterol, LDL, and HDL. It is also associated with decreases in free fatty acids. Increases in LDL occurred primarily during the first 1 to 2 months of therapy with AVANDIA and LDL levels remained elevated above baseline throughout the trials. In contrast, HDL continued to rise over time. As a result, the LDL/HDL ratio peaked after 2 months of therapy and then appeared to decrease over time.
Cơ Chế Tác Dụng : Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is marketed by the pharmaceutical company GlaxoSmithKline as a stand-alone drug (Avandia) and in combination with metformin (Avandamet) or with glimepiride (Avandaryl). Like other thiazolidinediones, the mechanism of action of rosiglitazone is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPARγ. Rosiglitazone is a selective ligand of PPARγ, and has no PPARα-binding action. Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFκB) levels fall and inhibitor (IκB) levels increase in patients on rosiglitazone. Recent research has suggested that rosiglitazone may also be of benefit to a subset of patients with Alzheimer's disease not expressing the ApoE4 allele. This is the subject of a clinical trial currently underway. Rosiglitazone acts as a highly selective and potent agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR-gamma receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In this way, rosiglitazone enhances tissue sensitivity to insulin.
Dược Động Học :
▧ Absorption :
The absolute bioavailability of rosiglitazone is 99%. Peak plasma concentrations are observed about 1 hour after dosing. Administration of rosiglitazone with food resulted in no change in overall exposure (AUC), but there was an approximately 28% decrease in Cmax and a delay in Tmax (1.75 hours). These changes are not likely to be clinically significant; therefore, rosiglitazone may be administered with or without food. Maximum plasma concentration (Cmax) and the area under the curve (AUC) of rosiglitazone increase in a dose-proportional manner over the therapeutic dose range.
▧ Volume of Distribution :
* 17.6 L [oral volume of distribution Vss/F] * 13.5 L [population mean, pediatric patients]
▧ Protein binding :
99.8% bound to plasma proteins, primarily albumin.
▧ Metabolism :
Hepatic. Rosiglitazone is extensively metabolized in the liver to inactive metabolites via N-demethylation, hydroxylation, and conjugation with sulfate and glucuronic acid. In vitro data have shown that Cytochrome (CYP) P450 isoenzyme 2C8 (CYP2C8) and to a minor extent CYP2C9 are involved in the hepatic metabolism of rosiglitazone.
▧ Route of Elimination :
Following oral or intravenous administration of [14C]rosiglitazone maleate, approximately 64% and 23% of the dose was eliminated in the urine and in the feces, respectively.
▧ Half Life :
3-4 hours (single oral dose, independent of dose)
▧ Clearance :
* Oral clearance (CL) = 3.03 ± 0.87 L/hr [1 mg Fasting] * Oral CL = 2.89 ± 0.71 L/hr [2 mg Fasting] * Oral CL = 2.85 ± 0.69 L/hr [8 mg Fasting] * Oral CL = 2.97 ± 0.81 L/hr [8 mg Fed] * 3.15 L/hr [Population mean, Pediatric patients]
Độc Tính : Side effects include fluid retention, congestive heart failure (CHF), liver disease
Chỉ Định : Rosiglitazone is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Tương Tác Thuốc :
  • Avanafil Co-administration with avanafil resulted in an approximate 2.0% increase in AUC0-inf and 14% decrease in Cmax of rosiglitazone.
  • Colesevelam Bile Acid Sequestrants may decrease the absorption of Antidiabetic Agents (Thiazolidinedione). Separate the dosing of bile acid sequestrants and thiazolidinediones by at least 2 hours. Monitor for reduced effects of the antidiabetic agents.
  • Gemfibrozil Increases the effect and toxicity of rosiglitazone/pioglitazone
  • Ketoconazole Ketoconazole increases the effect of rosiglitazone
  • Rifampicin Rifampin reduces levels and efficacy of rosiglitazone
  • Somatropin recombinant Somatropin may antagonize the hypoglycemic effect of rosiglitazone. Monitor for changes in fasting and postprandial blood sugars.
  • Tretinoin The moderate CYP2C8 inhibitor, Rosiglitazone, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Rosiglitazone is initiated, discontinued to dose changed.
Liều Lượng & Cách Dùng : Tablet - Oral - 2 mg, 4 mg, 8 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Avandia 2 mg tablet
    Giá bán buôn : USD >3.22
    Đơn vị tính : tablet
  • Biệt dược thương mại : Avandia 4 mg tablet
    Giá bán buôn : USD >4.72
    Đơn vị tính : tablet
  • Biệt dược thương mại : Avandia 8 mg tablet
    Giá bán buôn : USD >8.69
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty : GlaxoSmithKline
    Sản phẩm biệt dược : Avandia
  • Công ty : Werrick
    Sản phẩm biệt dược : Blutab
  • Công ty : Hasan
    Sản phẩm biệt dược : DH-Rosidia
  • Công ty : Elea
    Sản phẩm biệt dược : Diaben
  • Công ty : Farmindustria
    Sản phẩm biệt dược : Diaglinex
  • Công ty : Craveri
    Sản phẩm biệt dược : Gaudil
  • Công ty : Denver
    Sản phẩm biệt dược : Gliximina
  • Công ty : Hisun
    Sản phẩm biệt dược : Naidi
  • Công ty : Torrent
    Sản phẩm biệt dược : Rogelin
  • Công ty : Gedeon Richter
    Sản phẩm biệt dược : Roglit
  • Sản phẩm biệt dược : Romerol
  • Công ty : Delta
    Sản phẩm biệt dược : Rosit
  • Công ty : Garmisch
    Sản phẩm biệt dược : Rosix
  • Công ty : Trima
    Sản phẩm biệt dược : Rossini
  • Công ty : Square
    Sản phẩm biệt dược : Sensulin
  • Công ty : Hengrui
    Sản phẩm biệt dược : Sheng Ao
  • Sản phẩm biệt dược : Sheng Min
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00412
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00596
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=28681
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0029-3158-18
PharmGKB
http://www.pharmgkb.org/drug/PA451283
Wikipedia
http://en.wikipedia.org/wiki/Rosiglitazone
RxList
http://www.rxlist.com/cgi/generic2/rosigl.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cx1532.shtml
Drugs.com
http://www.drugs.com/cdi/rosiglitazone.html
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