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

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).

Comparative Pharmacokinetics/Pharmacodynamics of Fixed-Dose Combination of Esomeprazole and Calcium Carbonate (AD-206) to the Conventional Esomeprazole

“…This trend was observed both after a single- and multiple-dose at steady state and in other fixed dose combinations of PPIs and NaHCO 3 . 14 , 15 Previous studies indicated that the gastric emptying rate increases as the size of the non-disintegrating drugs gets smaller. 22 , 23 Similarly, formulations developed for faster disintegration compared to the conventional ones showed a more rapid absorption in several clinical studies.…”

“…Percent decrease from baseline in the integrated acidity was used as a parameter for comparing the PD effects in previous studies. 15 , 16 , 34 It compares the acidity of the baseline and after a single- or multiple-dose. Considering that only about 2/3 of the proton pumps are inhibited after a single PPI dose, anticipation of the variability of the parameter after a single-dose was expected to be demanding.…”

“…14 Since its successful launch, there have been efforts to develop a combination of various PPIs with various antacid salts. 15,16 AD-206 is a fixed-dose combination of esomeprazole with 600 mg of calcium carbonate (CaCO 3 ) developed by Addpharma Pharmaceutical Corp, Korea. This is the first fixed dose combination of PPI with CaCO 3 as the antacid counterpart.…”

“… 14 Since its successful launch, there have been efforts to develop a combination of various PPIs with various antacid salts. 15 , 16 …”

“…Percent decrease from baseline in the integrated acidity was used as a parameter for comparing the PD effects in previous studies. 15,16,34 It compares the acidity of the baseline and after a single-or multiple-dose. Considering that…”