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

Abstract

Purpose: Proton pump inhibitors (PPIs) are used for the treatment of acid-related disorders. Demands for enhanced stability and faster onset led to the development of AD-206, a fixeddose combination of a PPI (esomeprazole) with an antacid salt (calcium carbonate). This study compared the pharmacokinetics (PKs) and pharmacodynamics (PDs) of AD-206 (Addpharma) with conventional esomeprazole (Nexium ® , AstraZeneca). Materials and Methods:A randomized, open-label, two-treatment, two-sequence crossover study was conducted with 2 different doses of esomeprazole at 20 and 40 mg with a fixed calcium carbonate dose of 600 mg in AD-206. Forty-four subjects were included in each dose group and randomly received either AD-206 or the conventional esomeprazole for 7 consecutive days in each period. After a single-and multiple-dose, blood samples for the PK analysis were analyzed, and 24-hour intragastric pH monitoring was conducted. Results:The systemic exposure of esomeprazole after a multiple-dose of AD-206 was similar to that of the conventional esomeprazole in both doses, but the time to reach the peak concentration was faster in AD-206. The percentage decrease from baseline in the integrated gastric acidity for a 24-hour interval after the dose was not significantly different between the AD-206 and the conventional esomeprazole after a single-and multiple-dose for both doses, and the time to reach pH 4 was faster for AD-206. Conclusion: AD-206 showed a similar systemic exposure and suppression of gastric acid secretion after a multiple-dose compared to the conventional esomeprazole.

Indirect spectroscopic determination of esomeprazole using malachite green dye in the presence of N-bromosuccinimide

“…)1( . Esomeprazole (ESO) is a proton pump inhibitor (PPI) (1) because it inhibits gastric acid secretion (3,2) ., including Zollinger-Ellison syndrome, as well as the treatment and prevention of gastric and duodenal ulcers and erosive esophagitis (4,5) and also works to eliminate stomach germs (helicobacter pylori) and heartburn (6) .…”

Pharmacokinetics of Esomeprazole Magnesium After Single Oral Doses in Healthy Subjects: Bioequivalence Study and Food Effects

“…5 Acid control for GERD patients improved considerably after the novel PPI esomeprazole was introduced to the market in 2001 in the United States and major European countries. 6 It has been confirmed that the food effect influences the pharmacokinetics of esomeprazole due to variability in stomach emptying and stimulation by bile flow, which causes changes in drug metabolism, and physical or chemical drug interactions. The pharmacodynamic (PD) effect of esomeprazole, including inhibition of gastric acid secretion and increase in the duration of time with intragastric pH > 4.0, correlates with the area under the concentration-time curve (AUC).…”

“…5 They covalently bind with the H + , K + -ATPase enzyme and irreversibly inactivate the proton pump. 5,6 Esomeprazole, as the S-enantiomer of omeprazole and the first single optical isomer in the PPI family, 7 is widely used for GERD. Furthermore, esomeprazole has a good pharmacokinetic (PK) profile in the gastrointestinal tract 8 as its peak plasma concentration (C max ) may be attained within 1-2 hours after oral administration with higher and more consistent bioavailability than omeprazole.…”

“…Proton pump inhibitors (PPIs) are the most direct and successful medications for treating acid‐related disorders 5 . They covalently bind with the H + , K + ‐ATPase enzyme and irreversibly inactivate the proton pump 5,6 . Esomeprazole, as the S‐enantiomer of omeprazole and the first single optical isomer in the PPI family, 7 is widely used for GERD.…”

“…This provides the rationale for its superior control of gastric acid secretion and improved clinical efficacy compared with previous PPIs 5 . Acid control for GERD patients improved considerably after the novel PPI esomeprazole was introduced to the market in 2001 in the United States and major European countries 6 …”