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: 24-hr pH monitoring; esomeprazole; immediate-release esomeprazole; sodium bicarbonate.

Conflict of interest statement

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.

© 2019 Kim et al.

Figures

Figure 1

Mean plasma concentration-time profiles (A) after a single administration on day 1 and (B) after multiple administrations on day 7. Notes: The vertical bars represent SD. Reference, esomeprazole 20 mg once daily for 7 days. Test, esomeprazole 20 mg/sodium bicarbonate 800 mg once daily for 7 days.

Figure 2

Median intragastric pH over a 24-hr interval with esomeprazole 20 mg/sodium bicarbonate 800 mg (test) or esomeprazole 20 mg (reference) at baseline, (A) after a single administration on day 1 and (B) after multiple administrations on day 7. Notes: Reference, esomeprazole 20 mg once daily for 7 days. Test, esomeprazole 20 mg/sodium bicarbonate 800 mg once daily for 7 days.

Figure 3

Median intragastric pH within 2 hrs with esomeprazole 20 mg/sodium bicarbonate 800 mg (test) or esomeprazole 20 mg (reference) at baseline, (A) after a single administration on day 1 and (B) after multiple administrations on day 7. Notes: Reference, esomeprazole 20 mg once daily for 7 days. Test, esomeprazole 20 mg/sodium bicarbonate 800 mg once daily for 7 days.

Figure 4

Mean percentage (%) of time with gastric pH >4 over a 24-hr period following treatment with esomeprazole 20 mg/sodium bicarbonate 800 mg (test) or esomeprazole 20 mg (reference) or at baseline. Notes: The vertical bars represent SD. Reference, esomeprazole 20 mg once daily for 7 days. Test, esomeprazole 20 mg/sodium bicarbonate 800 mg once daily for 7 days.