Characteristics of the Novel Potassium-Competitive Acid Blocker Vonoprazan Fumarate (TAK-438).
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.



This review project, including the publication of this article, was funded by Takeda Pharmaceutical Company Limited.
Global Medical Affairs Japan Department, Takeda Pharmaceutical Co., Ltd., Tokyo, Japan. Kazuyoshi.otake@takeda.com.
Kazuyoshi
K
Otake
Clinical Science, Takeda Development Center Japan, Takeda Pharmaceutical Co., Ltd., Osaka, Japan.
Yuuichi
Y
Sakurai
Medicinal Chemistry Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co., Ltd., Kanagawa, Japan.
Haruyuki
H
Nishida
Drug Safety Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co., Ltd., Kanagawa, Japan.
Hideo
H
Fukui
Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co., Ltd., Kanagawa, Japan.
Yoshihiko
Y
Tagawa
Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co., Ltd., Kanagawa, Japan.
Hitomi
H
Yamasaki
Analytical Development Laboratories, CMC Center, Takeda Pharmaceutical Co., Ltd., Kanagawa, Japan.
Masatoshi
M
Karashima
Analytical Development Laboratories, CMC Center, Takeda Pharmaceutical Co., Ltd., Osaka, Japan.
Keiichi
K
Otsuka
Extra Value Generation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Co., Ltd., Kanagawa, Japan.
Nobuhiro
N
Inatomi
D005765:Gastrointestinal Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D005767:Gastrointestinal Diseases / Q000188:drug therapy*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011758:Pyrroles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*
C552956:1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; D005765:Gastrointestinal Agents; D011758:Pyrroles; D013449:Sulfonamides
Acid-related diseases; Gastroenterology; Helicobacter pylori eradication; Lansoprazole; PPI; Potassium-competitive acid blockers; Proton pump inhibitor; Reflux esophagitis; TAK-438; Vonoprazan