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).