Vonoprazan for treatment of gastroesophageal reflux: pharmacodynamic and pharmacokinetic considerations

ABSTRACT

Introduction: 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.

KEYWORDS:

• Vonoprazan
• gastro-esophageal reflux disease
• GERD
• pharmacokinetics
• P-CABs

Article highlights

• About 30-40% of gastro-esophageal reflux disease (GERD) patients report an inadequate response to proton pump inhibitors drugs due to their suboptimal pharmacological profiles.

• Recently, a new synthesized Potassium-competitive acid blocker, Vonoprazan, has been developed by Takeda Pharmaceuticals with preliminary data showing higher suppression of gastric acid secretion and similar efficacy as well as safety as compared to lansoprazole in GERD patients.

• At variance from all the available PPIs, vonoprazan acts directly on H+,K+-ATPase irrespectively of their activity, providing a fast onset of action without requiring acid activation and specific timing with respect to food intake.

• Clinical and pharmacological investigations have confirmed a more rapid, potent and prolonged inhibition of acid secretion by vonoprazan, including a better nighttime acid control, as compared with PPIs, with a less antisecretory variability and a lower risk of drug interactions among patients.

• First clinical data in patients with erosive esophagitis (EE) have shown that the healing rate after two weeks of treatment with vonoprazan was higher than lansoprazole, with the proportion of patients with healed EE displaying a higher trend in the vonoprazan group, in patients with more severe esophagitis.

• Further studies investigating the efficacy and safety in the long-term of vonoprazan in patients with acid-related disorders are required.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded