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药品详细

Rosiglitazone(罗格列酮)

化学结构式图
中文名
罗格列酮
英文名
Rosiglitazone
分子式
C18H19N3O3S
化学名
5-[(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione
分子量
Average: 357.427
Monoisotopic: 357.114712179
CAS号
122320-73-4
ATC分类
A10B Oral Blood Glucose Lowering Drugs, Excl. Insulins
药物类型
small molecule
阶段
approved
商品名
Avandia;Rosiglizole;
同义名
Rosigliazone maleate;rosiglitazone;Rosiglitazone maleate;
基本介绍

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.

生产厂家
  • GlaxoSmithKline
  • Sb pharmco puerto rico inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Mohanty P, Aljada A, Ghanim H, Hofmeyer D, Tripathy D, Syed T, Al-Haddad W, Dhindsa S, Dandona P: Evidence for a potent antiinflammatory effect of rosiglitazone. J Clin Endocrinol Metab. 2004 Jun;89(6):2728-35. Pubmed
  2. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O’Neill MC, Zinman B, Viberti G: Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006 Dec 7;355(23):2427-43. Epub 2006 Dec 4. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenylpropylamines
Substructures
  • Carboxylic Acids and Derivatives
  • Phenols and Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Pyridines and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aminopyridines and Derivatives
  • Thiazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Thiazolidines
  • Anisoles
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Phenyl Esters
适应症
Diabetes 糖尿病;
药理
Indication For the treatment of Type II diabetes mellitus
Pharmacodynamics Rosiglitazone, a member of the drug group known as the thiazolidinediones or "insulin sensitizers", is not chemically or functionally related to the alpha-glucosidase inhibitors, the biguanides, or the sulfonylureas. Rosiglitazone targets insulin resistance and, hence, is used alone or with metformine or sulfonylurea to improve glycemic control in patients with type 2 diabetes mellitus.
Mechanism of action Rosiglitazone acts as an 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.
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.
Volume of distribution
  • 6 L
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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Rosiglitazone
N-desmethylrosiglitazone Details
Rosiglitazone
para-hydroxyrosiglitazone Details
Rosiglitazone
ortho-hydroxyrosiglitazone Details
Rosiglitazone
    		N-desmethyl-o-hydroxyroziglitazone Details
    Rosiglitazone
      		N-desmethyl-o-O-sulfate rosizglitazone Details
      Rosiglitazone
        		N-desmethyl-p-hydroxyroziglitazone Details
        Rosiglitazone
          		N-desmethyl-p-O-sulfate rosizglitazone Details
          Rosiglitazone
            		N-despyridinyl rosiglitazone Details
            Rosiglitazone
              		o-O-glucuronide rosiglitazone Details
              Rosiglitazone
                		o-O-sulfate rosiglitazone Details
                Rosiglitazone
                  		p-O-glucuronide rosiglitazone Details
                  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
                  Clearance
                  • Oral 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]
                  Toxicity Side effects include fluid retention, congestive heart failure (CHF), liver disease
                  Affected organisms
                  • Humans and other mammals
                  Pathways Not Available
                  理化性质
                  Properties
                  State solid
                  Experimental Properties
                  Property Value Source
                  melting point 122-123 °C Not Available
                  logP 2.4 Not Available
                  Predicted Properties
                  Property Value Source
                  water solubility 3.80e-02 g/l ALOGPS
                  logP 2.95 ALOGPS
                  logP 2.45 ChemAxon
                  logS -4 ALOGPS
                  pKa (strongest acidic) 6.84 ChemAxon
                  pKa (strongest basic) 6.23 ChemAxon
                  physiological charge -1 ChemAxon
                  hydrogen acceptor count 5 ChemAxon
                  hydrogen donor count 1 ChemAxon
                  polar surface area 71.53 ChemAxon
                  rotatable bond count 7 ChemAxon
                  refractivity 97.79 ChemAxon
                  polarizability 37.79 ChemAxon
                  药物相互作用
                  Drug Interaction
                  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
                  Rifampin 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.
                  食物相互作用
                  Not Available

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