The safety, pharmacodynamics, and pharmacokinetics of immediate-release formulation containing esomeprazole 20 mg/sodium bicarbonate 800 mg in healthy adult male

Abstract

Background

Esomeprazole is the most effective treatment for acid-related disorders and is widely used with enteric coating due to rapid degradation in the acidic environment. However, the enteric-coated formulation delays absorption and onset of action. To overcome this limitation, an immediate-release formulation containing esomeprazole 20 mg and sodium bicarbonate 800 mg (IR-ESO) was developed.

Purpose

To evaluate the safety, pharmacokinetics (PK), and pharmacodynamics of IR-ESO compared to those of esomeprazole 20 mg (ESO).

Methods

A randomized, open-label, multiple-dose, two-treatment, two-sequence crossover study was conducted in 40 healthy male subjects. Subjects received either IR-ESO or ESO for 7 days. After single and multiple dosing, blood samples were collected for PK analysis, and intragastric pH was assessed by 24-hr pH monitoring.

Results

Plasma esomeprazole exposure of IR-ESO was similar to that of ESO after single and multiple dosing. Time to peak concentration of IR-ESO (0.50–0.75 hr) was shorter than that of ESO (1.25–1.50 hr). Percentage changes in 24-hr integrated gastric acidity from baseline for IR-ESO were similar to those for ESO. In addition, mean time to maintain gastric pH >4 for 24 hr was similar for both drugs (IR-ESO 55.5–69.9% vs ESO 56.8–70.2%). Evaluation of time to first reach pH 4 after dosing indicated that IR-ESO showed a faster onset than ESO. All subjects found the drug tolerable, and there were no significant differences in adverse events between two drugs.

Conclusion

This study showed that IR-ESO produced a rapid, safe and sustained gastric acid suppression (ClinicalTrials.gov: NCT03211143).

Keywords:

• sodium bicarbonate
• immediate-release esomeprazole
• esomeprazole
• 24-hr pH monitoring

Acknowledgments

We would like to thank the staff at Severance Hospital Clinical Trials Center for assistance for conducting this study. This study was sponsored by Chong Kun Dang Pharmaceutical Corp., Seoul, Korea, and supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI17C1913).

Data availability

The raw data of this study will not be shared because of confidentiality.

Author contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

Shin Jung Park is a full-time employee of Chong Kun Dang Pharmaceutical Corp. The authors report no other conflicts of interest in this work.