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对胰高血糖素样肽-1受体激动剂的药物设计和药代动力学特征的洞察。

An Insight into Pharmaceutical Design and Pharmacokinetic Characteristics of GLP-1 RAs.

作者信息

Zayed Mohamed F, Khyat Nada O, Alsibyani Rawan W, Alshami Rahaf Z, Alsubahi Ramzyah A, Alamoudi Mariam K

机构信息

Pharmaceutical Sciences Department, Fakeeh College for Medical Sciences, Jeddah 21461, Saudi Arabia.

Bachelor of Science of Doctor of Pharmacy Program, Fakeeh College for Medical Sciences, Jeddah 21461 Saudi Arabia.

出版信息

Curr Pharm Des. 2025 Aug 11. doi: 10.2174/0113816128375766250720234005.

Abstract

INTRODCUTION

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are among the most effective treatments for type 2 diabetes mellitus (T2DM). GLP-1 RAs stimulate pancreatic receptors, improving glycemia by boosting insulin secretion while decreasing glucagon secretion. GLP-1 receptors are present in pancreatic tissue. They are also found in extra-pancreatic tissue and have been shown to reduce body weight while also protecting the heart and endothelial cells. The most prevalent types of GLP-1 RAs can be injected twice daily (exenatide), once daily (lixisenatide and liraglutide), or once weekly (albiglutide, dulaglutide, exenatide once, semaglutide, tirzepatide). GLP-1 receptor agonists also reduce gastric emptying, preventing substantial post-meal glycaemic increases. Many publications have been written regarding GLP-1 RAs, covering various features of this family. However, the purpose of this study is to investigate the pharmacological design models and pharmacokinetic characteristics of the most regularly used members of this class, as well as to highlight contemporary developments in GLP-1 RAs. It also describes the physicochemical features, techniques of manufacture, the effects of molecular structure, and structural modifications on pharmacological activity.

METHODS

The literature review was completed using a structured approach to identify and integrate relevant literature. It involved a broad search of reputable medical databases using inclusion and exclusion criteria.

RESULT

They are classified as short-acting or long-acting based on the length of their action. Short-acting GLP-1 RAs and long-acting GLP-1 RAs have differing efficacy profiles. Furthermore, the methods of administration, mode of action, and side effects of these medications are relevant to their pharmacological design and pharmacokinetic properties.

DISCUSSION

The treatment of type 2 diabetes and obesity has evolved with the advent of GLP-1 RAs. These drugs have a multifaceted approach, emphasizing glycemic regulation, weight loss, and reduction of cardiovascular risk. Their unique mode of action, strong safety profile, and ability to be individualized according to each patient's needs make them a valuable therapeutic option in the management of metabolic disorders. Their pharmacological activities are also influenced by their different structural and pharmacokinetic properties.

CONCLUSION

GLP-1 RAs have a complex strategy due to their pharmacological nature. The variations in their design have led to various members with varying pharmacodynamic and pharmacokinetic features.

摘要

引言

胰高血糖素样肽-1受体激动剂(GLP-1 RAs)是2型糖尿病(T2DM)最有效的治疗药物之一。GLP-1 RAs刺激胰腺受体,通过促进胰岛素分泌同时减少胰高血糖素分泌来改善血糖水平。GLP-1受体存在于胰腺组织中。它们也存在于胰腺外组织中,并且已被证明可减轻体重,同时保护心脏和内皮细胞。最常见的GLP-1 RAs类型可以每日注射两次(艾塞那肽)、每日注射一次(利司那肽和利拉鲁肽)或每周注射一次(阿必鲁肽、度拉鲁肽、长效艾塞那肽、司美格鲁肽、替尔泊肽)。GLP-1受体激动剂还可减少胃排空,防止餐后血糖大幅升高。关于GLP-1 RAs已经有许多出版物,涵盖了该类药物的各种特征。然而,本研究的目的是研究该类最常用药物的药理设计模型和药代动力学特征,并突出GLP-1 RAs的当代发展。它还描述了其物理化学特征、制造技术、分子结构的影响以及结构修饰对药理活性的影响。

方法

采用结构化方法完成文献综述,以识别和整合相关文献。这涉及使用纳入和排除标准对著名医学数据库进行广泛搜索。

结果

根据其作用时长,它们被分类为短效或长效。短效GLP-1 RAs和长效GLP-1 RAs具有不同的疗效特征。此外,这些药物的给药方法、作用方式和副作用与其药理设计和药代动力学特性相关。

讨论

随着GLP-1 RAs的出现,2型糖尿病和肥胖症的治疗方法不断发展。这些药物具有多方面的作用,强调血糖调节、体重减轻和心血管风险降低。它们独特的作用方式、强大的安全性以及根据每个患者需求进行个体化治疗的能力,使其成为代谢紊乱管理中有价值的治疗选择。它们的药理活性也受到其不同结构和药代动力学特性的影响。

结论

由于其药理性质,GLP-1 RAs具有复杂的策略。其设计的差异导致了具有不同药效学和药代动力学特征的各种药物。

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