Zastaprazan associated with rapid and potent suppression of gastric acid secretion

After a single oral dose of up to 60 mg and successive oral doses of up to 40 mg, zastaprazan was well tolerated and safe, says an article published in Alimentary Pharmacology and Therapeutics.

A new potassium-competitive acid blocker being researched for the treatment of conditions caused by excess acid is called zastaprazan (JP-1366). It has a favorable preclinical safety and effectiveness profile. Inyoung Hwang and colleagues undertook this study to look at the pharmacodynamics and pharmacokinetics of zastaprazan as well as its safety and tolerability.

On healthy Korean male volunteers, an open-label, randomized, placebo- and active-controlled, single and multiple ascending dosage clinical study was carried out. Serial blood and urine samples were taken to evaluate the pharmacokinetics, while intragastric pH and serum gastrin levels were assessed to evaluate the pharmacodynamics. To investigate genetic variations that may have an impact on pharmacodynamics and pharmacokinetics, pharmacogenomic assessment was carried out. Hepatotoxicity, along with safety and acceptability, were assessed.

The key findings of this study were;

1. As zastaprazan dosage rose, stomach acid output was suppressed more and more.

2. In comparison to esomeprazole 40 mg (72.06%), zastaprazan 20 mg (85.19%) and 40 mg (91.84%) had a similar or higher proportion of times when the stomach pH was over 4 (%Time pH >4).

3. Zastaprazan had a half-life of 6–10 hours and was quickly absorbed within 2 hours.

4. No genetic variation of drug transporters or drug metabolizing enzymes, such as CYP2C19, was discovered by pharmacogenomic study to be connected to the exposure to zastaprazan.

5. Zastaprazan was well tolerated, and ratings of safety and tolerability did not alter in a clinically relevant way.

Potassium-competitive acid blocker called zastaprazan may expand the range of treatments available to people with acid-related disorders since it seems to have a reasonable risk-benefit profile. Additionally, it revealed a quick, effective inhibition of stomach acid output. Patients with disorders associated with acidity can be treated with zastaprazan due to its favorable pharmacodynamic and pharmacokinetic properties.

Reference:

Hwang, I., Ji, S. C., Oh, J., Kim, H., Cha, H., Kim, J., Lee, C., Yu, K., & Lee, S. (2023). Randomised clinical trial: Safety, tolerability, pharmacodynamics and pharmacokinetics of zastaprazan (JP‐1366), a novel potassium‐competitive acid blocker, in healthy subjects. In Alimentary Pharmacology & Therapeutics (Vol. 57, Issue 7, pp. 763–772). Wiley. https://doi.org/10.1111/apt.17406