Otake Kazuyoshi, Sakurai Yuuichi, Nishida Haruyuki, Fukui Hideo, Tagawa Yoshihiko, Yamasaki Hitomi, Karashima Masatoshi, Otsuka Keiichi, Inatomi Nobuhiro
Global Medical Affairs Japan Department, Takeda Pharmaceutical Co., Ltd., Tokyo, Japan.
Clinical Science, Takeda Development Center Japan, Takeda Pharmaceutical Co., Ltd., Osaka, Japan.
Adv Ther. 2016 Jul;33(7):1140-57. doi: 10.1007/s12325-016-0345-2. Epub 2016 Jun 10.
UNLABELLED: Proton pump inhibitors (PPIs) are widely prescribed as first-line therapy for the treatment of acid-related diseases, such as peptic ulcers and gastro-esophageal reflux disease, and for the eradication of Helicobacter pylori. However, the therapeutic efficacy of conventional PPIs is considered limited because: (1) they are unstable under acidic conditions and require an enteric-coated formulation in clinical use; (2) they show high interindividual variability in pharmacokinetics due to genetic polymorphisms of cytochrome P450 (CYP) 2C19 metabolism; (3) they have a relatively slow onset of pharmacological action and may require several doses to achieve optimal acid suppression and symptom relief; and (4) they often do not provide stable suppression of gastric acid secretion over 24 h. Vonoprazan fumarate (TAK-438, hereinafter referred to as "vonoprazan") is a new potassium-competitive acid blocker (P-CAB) developed to resolve the above limitations of conventional PPIs. Various physicochemical data have shown that vonoprazan has a high solubility and stability over a broad pH range in aqueous conditions. In addition, vonoprazan has a more potent and longer-lasting acid suppression effect than the conventional PPI, lansoprazole. Preclinical pharmacokinetic studies have shown that vonoprazan is accumulated and retained in the stomach for more than 24 h, even after it is eliminated from the plasma. From these findings, we propose that vonoprazan, which possesses a novel mode of action, can improve on the outcomes seen with conventional PPI-based treatments for acid-related diseases. FUNDING: This review project, including the publication of this article, was funded by Takeda Pharmaceutical Company Limited.
未标注:质子泵抑制剂(PPIs)被广泛用作治疗酸相关疾病(如消化性溃疡和胃食管反流病)以及根除幽门螺杆菌的一线疗法。然而,传统质子泵抑制剂的治疗效果被认为是有限的,原因如下:(1)它们在酸性条件下不稳定,临床使用时需要肠溶包衣制剂;(2)由于细胞色素P450(CYP)2C19代谢的基因多态性,它们在药代动力学上表现出较高的个体间变异性;(3)它们的药理作用起效相对较慢,可能需要多次给药才能达到最佳的胃酸抑制和症状缓解效果;(4)它们通常无法在24小时内持续稳定地抑制胃酸分泌。富马酸沃克帕唑(TAK-438,以下简称“沃克帕唑”)是一种新开发的钾竞争性酸阻滞剂(P-CAB),旨在解决传统质子泵抑制剂的上述局限性。各种理化数据表明,沃克帕唑在水性条件下的广泛pH范围内具有高溶解度和稳定性。此外,沃克帕唑比传统质子泵抑制剂兰索拉唑具有更强、更持久的胃酸抑制作用。临床前药代动力学研究表明,即使沃克帕唑从血浆中消除后,它仍会在胃中蓄积并保留超过24小时。基于这些发现,我们提出,具有新型作用模式的沃克帕唑可以改善基于传统质子泵抑制剂治疗酸相关疾病的效果。 资助:本综述项目,包括本文的发表,由武田制药有限公司资助。
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