<br>普兰林肽作为胰岛素治疗的辅助药物：给药方面的挑战和最新进展,Journal of Pharmacology and Experimental Therapeutics

当前位置： X-MOL 学术 › J. Pharmacol. Exp. Ther. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

普兰林肽作为胰岛素治疗的辅助药物：给药方面的挑战和最新进展
Journal of Pharmacology and Experimental Therapeutics ( IF 3.1 ) Pub Date : 2024-01-01 , DOI: 10.1124/jpet.123.001679
Sai Pradyuth Kommera ₁ , Ankur Kumar ₁ , Deepak Chitkara ₁ , Anupama Mittal ₂

Affiliation

各种葡萄糖调节激素的失调导致糖尿病患者胰岛素单药治疗失败，原因有多种，包括严重低血糖、血糖高变性和微血管并发症风险增加。然而，普兰林肽作为胰岛素治疗的辅助剂可增强胰高血糖素抑制，从而改善血糖控制。临床研究表明，普兰林肽可改善 1 型和 2 型糖尿病患者的血糖控制、减少餐后血糖波动并促进体重减轻。尽管普兰林肽的临床益处已得到充分报道，但患者对该疗法的抵抗力仍然很高，因为普兰林肽和胰岛素必须分开注射。尽管市售胰岛素制剂通常在 60-90 分钟内达到峰值作用，但普兰林肽在给药后约 20-30 分钟达到峰值浓度。因此，由于外源性施用的普兰林肽和胰岛素的药代动力学存在显着差异，该疗法无法引起由内源性激素产生的作用。因此，已经采用了一些策略，例如通过使用二氧化硅等无机聚合物、聚己内酯等合成聚合物和脂质来延迟普兰林肽的释放。此外，还探索了非共价缀合、聚电解质络合以及使用两亲性赋形剂共同递送胰岛素和普兰林肽等方法来解决普兰林肽递送的问题并提高患者对治疗的依从性。这种方法可能会开创糖尿病管理的新时代，为患者提供多种选择来定制治疗并提高他们的生活质量。

"点击查看英文标题和摘要"

Pramlintide an Adjunct to Insulin Therapy: Challenges and Recent Progress in Delivery

Dysregulation of various glucoregulatory hormones lead to failure of insulin monotherapy in patients with diabetes mellitus due to various reasons, including severe hypoglycemia, glycemic hypervariability, and an increased risk of microvascular complications. However, pramlintide as an adjunct to insulin therapy enhances glucagon suppression and thereby offers improved glycemic control. Clinical studies have shown that pramlintide improves glycemic control, reduces postprandial glucose excursions, and promotes weight loss in patients with type 1 and type 2 diabetes. Although clinical benefits of pramlintide are well reported, there still exists a high patient resistance for the therapy, as separate injections for pramlintide and insulin must be administered. Although marketed insulin formulations generally demonstrate a peak action in 60–90 minutes, pramlintide elicits its peak concentration at around 20–30 minutes after administration. Thus, owing to the significant differences in pharmacokinetics of exogenously administered pramlintide and insulin, the therapy fails to elicit its action otherwise produced by the endogenous hormones. Hence, strategies such as delaying the release of pramlintide by using inorganic polymers like silica, synthetic polymers like polycaprolactone, and lipids have been employed. Also, approaches like noncovalent conjugation, polyelectrolyte complexation, and use of amphiphilic excipients for codelivery of insulin and pramlintide have been explored to address the issues with pramlintide delivery and improve patient adherence to the therapy. This approach may usher in a new era of diabetes management, offering patients multiple options to tailor their treatment and improve their quality of life.

更新日期：2024-01-02

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南