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沃克(富马酸伏诺拉生)用于治疗胃食管反流:药效学和药代动力学考量

Vonoprazan for treatment of gastroesophageal reflux: pharmacodynamic and pharmacokinetic considerations.

作者信息

Savarino Edoardo, Martinucci Irene, Furnari Manuele, Romana Chiara, Pellegatta Gaia, Moscatelli Alessandro, Bodini Giorgia, Marabotto Elisa, Savarino Vincenzo, de Bortoli Nicola, Blandizzi Corrado

机构信息

a Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology , University of Padua , Padua , Italy.

b Division of Gastroenterology, Department of Internal Medicine , University of Pisa , Pisa , Italy.

出版信息

Expert Opin Drug Metab Toxicol. 2016 Nov;12(11):1333-1341. doi: 10.1080/17425255.2016.1214714. Epub 2016 Aug 8.

Abstract

About 30-40% of GERD patients report an inadequate response to proton pump inhibitors (PPIs) due to their suboptimal pharmacological profiles. Recently, a new synthesized P-CABs, vonoprazan, showed higher suppression of gastric acid secretion as compared to lansoprazole. Areas covered: This review provides an update on the pharmacokinetic properties of vonoprazan and their correlates with pharmacodynamics; preliminary data on the therapeutic efficacy of vonoprazan as compared to lansoprazole in GERD patients Expert opinion: At variance from all available PPIs, vonoprazan acts directly on H+,K+-ATPase irrespectively of its activity, providing a fast onset of action without requiring acid activation and specific administration timing. Clinical and pharmacological investigations have confirmed a more rapid, potent and prolonged inhibition of acid secretion, including a better nighttime acid control, and a less antisecretory variability, as compared with PPIs. Preliminary data in patients with erosive esophagitis (EE) have shown the non-inferiority of vonoprazan to lansoprazole in terms of symptom relief and healing rate. Since these pharmacokinetic advantages, it is expected that it will have a significant favorable impact on GERD management. However, the clinical use of vonoprazan raises also some issues about its efficacy and safety in the long-term that deserve verification and careful investigation.

摘要

约30%-40%的胃食管反流病(GERD)患者报告称,由于质子泵抑制剂(PPI)的药理特性欠佳,其治疗效果不理想。最近,一种新合成的钾离子竞争性酸阻滞剂(P-CAB)沃克吕唑,与兰索拉唑相比,对胃酸分泌的抑制作用更强。涵盖领域:本综述介绍了沃克吕唑的药代动力学特性及其与药效学的相关性;与兰索拉唑相比,沃克吕唑在GERD患者中的治疗效果的初步数据。专家观点:与所有现有的PPI不同,沃克吕唑直接作用于H+,K+-ATP酶,无论其活性如何,起效迅速,无需酸激活,给药时间也无特殊要求。临床和药理学研究证实,与PPI相比,沃克吕唑对胃酸分泌的抑制作用更快、更强、更持久,包括更好地控制夜间胃酸分泌,且抑酸变异性更小。糜烂性食管炎(EE)患者的初步数据显示,在缓解症状及愈合率方面,沃克吕唑不劣于兰索拉唑。鉴于这些药代动力学优势,预计它将对GERD的治疗产生重大积极影响。然而,沃克吕唑在临床应用中,其长期疗效和安全性也存在一些问题,值得验证和仔细研究。

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