药品详细
Troglitazone(曲格列酮)
化学结构式图
中文名
曲格列酮
英文名
Troglitazone
分子式
Not Available
化学名
5-({4-[(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-yl)methoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione
分子量
Average: 441.54
Monoisotopic: 441.160993669
Monoisotopic: 441.160993669
CAS号
97322-87-7
ATC分类
A10B Oral Blood Glucose Lowering Drugs, Excl. Insulins
药物类型
small molecule
阶段
商品名
Noscal;Prelay;Resulin;Rezulin;Romglizone;Romozin;
同义名
基本介绍
Troglitazone was withdrawn in 2000 due to risk of hepatotoxicity. It was superseded by pioglitazone and rosiglitazone.
生产厂家
- Pfizer pharmaceuticals ltd
- Sankyo usa corp
封装厂家
参考
| Synthesis Reference | Not Available |
| General Reference |
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剂型
| Form | Route | Strength |
|---|---|---|
| Tablet | Oral |
规格
化合物类型
| Type | small molecule |
| Classes |
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| Substructures |
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适应症
Diabetes 糖尿病;
药理
| Indication | For the treatment of Type II diabetes mellitus. It is used alone or in combination with a sulfonylurea, metformin, or insulin as an adjunct to diet and exercise. |
| Pharmacodynamics | Troglitazone is an oral antihyperglycemic agent which acts primarily by decreasing insulin resistance. Troglitazone is used in the management of type II diabetes (noninsulin-dependent diabetes mellitus (NIDDM) also known as adult-onset diabetes). It improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Troglitazone is not chemically or functionally related to either the sulfonylureas, the biguanides, or the g-glucosidase inhibitors. Troglitazone may be used concomitantly with a sulfonylurea or insulin to improve glycemic control. |
| Mechanism of action | Troglitazone is a thiazolidinedione antidiabetic agent that lowers blood glucose by improving target cell response to insulin. It has a unique mechanism of action that is dependent on the presence of insulin for activity. Troglitazone decreases hepatic glucose output and increases insulin dependent glucose disposal in skeletal muscle. Its mechanism of action is thought to involve binding to nuclear receptors (PPAR) that regulate the transcription of a number of insulin responsive genes critical for the control of glucose and lipid metabolism. Troglitazone is a ligand to both PPAR伪 and PPAR纬, with a highter affinity for PPAR纬. The drug also contains an 伪-tocopheroyl moiety, potentially giving it vitamin E-like activity. Troglitazone has been shown to reduce inflammation, and is associated with a decrase in nuclear factor kappa-B (NF-魏B) and a concomitant increase in its inhibitor (I魏B). NF-魏B is an important cellular transcription regulator for the immune response. Unlike sulfonylureas, troglitazone is not an insulin secretagogue. |
| Absorption | Absorbed rapidly. Food increases the extent of absorption by 30% to 85%. |
| Volume of distribution | Not Available |
| Protein binding | > 99% (primarily to serum albumin) |
| Metabolism |
A sulfate conjugate metabolite (Metabolite 1) and a quinone metabolite (Metabolite 3) have been detected in the plasma of healthy males. A glucuronide conjugate (Metabolite 2) has been detected in the urine and also in negligible amounts in the plasma. In healthy volunteers and in patients with type 2 diabetes, the steady-state concentration of Metabolite 1 is six to seven times that of troglitazone and Metabolite 3. In in vivo drug interaction studies, troglitazone has been shown to induce cytochrome P450 CYP3A4 at clinically relevant doses. |
| Route of elimination | Not Available |
| Half life | 16-34 hours |
| Clearance | Not Available |
| Toxicity | Not Available |
| Affected organisms |
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| Pathways | Not Available |
理化性质
| Properties | |||||||||||||||||||||||||||||||||||||
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| State | solid | ||||||||||||||||||||||||||||||||||||
| Melting point | 184-186 oC | ||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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药物相互作用
| Drug | Interaction |
|---|---|
| Cholestyramine | Decreases the effect of troglitazone |
| Cyclosporine | Troglitazone decreases the effect of the immunosuppressant |
| Ethinyl Estradiol | Possible loss of contracepitve effect |
| Norethindrone | Possible loss of contraceptive effect |
食物相互作用
Not Available
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