药品详细
Liraglutide (利拉鲁肽 )
化学结构式图
没有图片
中文名
利拉鲁肽
英文名
Liraglutide
分子式
Not Available
化学名
分子量
CAS号
204656-20-2
ATC分类
A10B Oral Blood Glucose Lowering Drugs, Excl. Insulins
药物类型
biotech
阶段
商品名
Victoza (Novo Nordisk);
同义名
NN 2211;NN2211;
基本介绍
Victoza contains liraglutide, an analog of human GLP-1 and acts as a GLP-1 receptor agonist. The peptide precursor of liraglutide, produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae, has been engineered to be 97% homologous to native human GLP-1 by substituting arginine for lysine at position 34. Liraglutide is made by attaching a C-16 fatty acid (palmitic acid) with a glutamic acid spacer on the remaining lysine residue at position 26 of the peptide precursor.
生产厂家
- Novo nordisk inc
封装厂家
参考
| Synthesis Reference | Not Available |
| General Reference |
|
剂型
| Form | Route | Strength |
|---|---|---|
| Solution | Subcutaneous | Multi-dose pen (0.6 mg, 1.2 mg, or 1.8 mg [6 mg/mL, 3 mL]) |
规格
化合物类型
| Type | biotech |
| Classes | Not Available |
| Substructures | Not Available |
适应症
Diabetes 糖尿病;
药理
| Indication | For use/treatment in diabetes mellitus type 2 and obesity. |
| Pharmacodynamics | Liraglutide is a once-daily GLP-1 derivative for the treatment of type 2 diabetes. GLP-1, in its natural form, is short-lived in the body (the half-life after subcutaneous injection is approximately one hour), so it is not very useful as a therapeutic agent. However, liraglutide has a half-life after subcutaneous injection of 11–15 hours, making it suitable for once-daily dosing. The prolonged action of liraglutide is achieved by attaching a fatty acid molecule at one position of the GLP-1 molecule, enabling it to bind to albumin within the subcutaneous tissue and bloodstream. The active GLP-1 is then released from albumin at a slow, consistent rate. Binding with albumin also results in slower degradation and reduced elimination of liraglutide from the circulation by the kidneys compared to GLP-1. |
| Mechanism of action | Liraglutide is an acylated human glucagon-like peptide-1 (GLP-1) receptor agonist, with a 97% amino acid sequence homology to endogenous human GLP-1(7-37). GLP-1(7-37) represents <20% of total circulating endogenous GLP-1. Like GLP-1(7-37), liraglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase by the stimulatory G-protein, Gs, in pancreatic beta cells. Liraglutide increases intracellular cyclic AMP (cAMP), leading to insulin release in the presence of elevated glucose concentrations. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia. Liraglutide also decreases glucagon secretion in a glucose-dependent manner. The mechanism of blood glucose lowering also involves a delay in gastric emptying. |
| Absorption | Following subcutaneous administration, maximum concentrations of liraglutide are achieved at 8-12 hours post dosing. The mean peak (Cmax) and total (AUC) exposures of liraglutide were 35 ng/mL and 960 ng·h/mL, respectively, for a subcutaneous single dose of 0.6 mg. After subcutaneous single dose administrations, Cmax and AUC of liraglutide increased proportionally over the therapeutic dose range of 0.6 mg to 1.8 mg. At 1.8 mg Victoza, the average steady state concentration of liraglutide over 24 hours was approximately 128 ng/mL. AUC0-∞ was equivalent between upper arm and abdomen, and between upper arm and thigh. AUC0-∞ from thigh was 22% lower than that from abdomen. However, liraglutide exposures were considered comparable among these three subcutaneous injection sites. Absolute bioavailability of liraglutide following subcutaneous administration is approximately 55%. |
| Volume of distribution | Not Available |
| Protein binding | Not Available |
| Metabolism |
During the initial 24 hours following administration of a single [3H]-liraglutide dose to healthy subjects, the major component in plasma was intact liraglutide. Liraglutide is endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination. |
| Route of elimination | Not Available |
| Half life | 11-15 hours following subcutaneous injection |
| Clearance | The mean apparent clearance following subcutaneous administration of a single dose of liraglutide is approximately 1.2 L/h |
| Toxicity | In a clinical trial, one patient with type 2 diabetes experienced a single overdose of Victoza 17.4 mg subcutaneous (10 times the maximum recommended dose). Effects of the overdose included severe nausea and vomiting requiring hospitalization. No hypoglycemia was reported. The patient recovered without complications. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. |
| Affected organisms |
|
| Pathways | Not Available |
理化性质
| Properties | |
|---|---|
| State | liquid |
| Melting point | Not Available |
| Experimental Properties | Not Available |
药物相互作用
| Drug | Interaction |
|---|---|
| Somatropin recombinant | Somatropin may antagonize the hypoglycemic effect of liraglutide. Monitor for changes in fasting and postprandial blood sugars. |
食物相互作用
Not Available
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