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药品详细

Pioglitazone(吡格列酮)

化学结构式图
中文名
吡格列酮
英文名
Pioglitazone
分子式
C19H20N2O3S
化学名
5-({4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione
分子量
Average: 356.439
Monoisotopic: 356.119463206
CAS号
111025-46-8
ATC分类
A10B Oral Blood Glucose Lowering Drugs, Excl. Insulins
药物类型
small molecule
阶段
approved
商品名
Actos;Actost;Glustin;
同义名
Pioglitazona [INN-Spanish];Pioglitazone [Ban:Inn];pioglitazone HCl;Pioglitazone Hydrochloride;Pioglitazonum [INN-Latin];
基本介绍

Pioglitazone is used for the treatment of diabetes mellitus type 2. Pioglitazone selectively stimulates nuclear receptor peroxisone proliferator-activated receptor gamma (PPAR-gamma). It modulates the transcription of the insulin-sensitive genes involved in the control of glucose and lipid metabolism in the lipidic, muscular tissues and in the liver.

生产厂家
  • Takeda pharmaceuticals north america inc
  • Takeda Pharmaceuticals North America, Inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Colca JR, McDonald WG, Waldon DJ, Leone JW, Lull JM, Bannow CA, Lund ET, Mathews WR: Identification of a novel mitochondrial protein (“mitoNEET”) cross-linked specifically by a thiazolidinedione photoprobe. Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E252-60. Epub 2003 Oct 21. Pubmed
  2. Paddock ML, Wiley SE, Axelrod HL, Cohen AE, Roy M, Abresch EC, Capraro D, Murphy AN, Nechushtai R, Dixon JE, Jennings PA: MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14342-7. Epub 2007 Aug 31. Pubmed
  3. Lincoff AM, Wolski K, Nicholls SJ, Nissen SE: Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007 Sep 12;298(10):1180-8. 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
  • Pyridines and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Thiazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Thiazolidines
  • Anisoles
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Imines
  • Phenyl Esters
适应症
Diabetes 糖尿病;
药理
Indication Treatment of Type II diabetes mellitus
Pharmacodynamics Pioglitazone, 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. Pioglitazone targets insulin resistance and, hence, is used alone or in combination with insulin, metformin, or asulfonylurea as an antidiabetic agent.
Mechanism of action Pioglitazone 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 increases the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In this way, pioglitazone both enhances tissue sensitivity to insulin and reduces hepatic gluconeogenesis. Thus, insulin resistance associated with type 2 diabetes mellitus is improved without an increase in insulin secretion by pancreatic β cells.
Absorption Following oral administration, in the fasting state, pioglitazone is first measurable in serum within 30 minutes, with peak concentrations observed within 2 hours. Food slightly delays the time to peak serum concentration to 3 to 4 hours, but does not alter the extent of absorption.
Volume of distribution
  • 0.63 ± 0.41 L/kg
Protein binding > 99%
Metabolism
Hepatic
Route of elimination Following oral administration, approximately 15% to 30% of the pioglitazone dose is recovered in the urine. Renal elimination of pioglitazone is negligible, and the drug is excreted primarily as metabolites and their conjugates. It is presumed that most of the oral dose is excreted into the bile either unchanged or as metabolites and eliminated in the feces.
Half life 3-7 hours
Clearance
  • apparent cl=5 – 7 L/h [oral administration]
Toxicity Hypogycemia; LD50=mg/kg (orally in rat)
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 183-184 °C Not Available
water solubility mg/mL Not Available
logP 2.3 Not Available
Predicted Properties
Property Value Source
water solubility 4.42e-03 g/l ALOGPS
logP 3.17 ALOGPS
logP 3.33 ChemAxon
logS -4.9 ALOGPS
pKa (strongest acidic) 6.66 ChemAxon
pKa (strongest basic) 5.6 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 68.29 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 97.39 ChemAxon
polarizability 37.91 ChemAxon
药物相互作用
Drug Interaction
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 Gemfibrozil may increase the effect and toxicity of pioglitazone.
Glucosamine Possibly hyperglycemia
Ketoconazole Ketoconazole increases the effect of pioglitazone
Mestranol Possible loss of contraceptive effect
Norethindrone Possible loss of contraceptive effect
Somatropin recombinant Somatropin may antagonize the hypoglycemic effect of pioglitazone. Monitor for changes in fasting and postprandial blood sugars.
Tamoxifen Pioglitazone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Tamsulosin Pioglitazone, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Pioglitazone is initiated, discontinued, or dose changed.
Tramadol Pioglitazone may decrease the effect of Tramadol by decreasing active metabolite production.
Tretinoin The moderate CYP2C8 inhibitor, Pioglitazone, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Pioglitazone is initiated, discontinued to dose changed.
食物相互作用
  • Take without regard to meals. Food slightly delays absorption rate but extent of absorption is not affected.

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