Published online Nov 26, 2020. doi: 10.12998/wjcc.v8.i22.5518
Peer-review started: June 5, 2020
First decision: July 25, 2020
Revised: August 6, 2020
Accepted: September 8, 2020
Article in press: September 8, 2020
Published online: November 26, 2020
Processing time: 173 Days and 4 Hours
Gastroesophageal reflux disease is the most common acid-related disease and also the most commonly diagnosed acid-related disease in the United States. The typical symptoms include heartburn and/or reflux. Without effective treatment, patients can develop serious complications, such as esophageal stricture, ulcers, or Barrett’s esophagus.
Esomeprazole is a new generation of proton pump inhibitors with faster absorption and a more vital ability to inhibit gastric acid secretion. The drug inhibits gastric acid secretion by explicitly inhibiting the H+/K+-ATPase in the gastric parietal cells, and is an alternative for proton pump inhibitors. At present, the pharmacokinetics and bioequivalence of esomeprazole in healthy Chinese subjects and the effects of food on the pharmacokinetics have not been well studied.
To observe the bioequivalence, tolerability, and safety of esomeprazole in healthy Chinese people.
Thirty-two healthy subjects in a fasting state and 32 in a fed state took the test or reference formulation Eso enteric-coated capsule by a four-cycle, two-sequence crossover of fasting/fed, self-controlled method. The liquid chromatography-mass spectrometry was used to determine the drug plasma concentration at 16 different time points within 12 h after drug administration. The pharmacokinetic parameters Cmax, area under the curve AUC0-t, and AUC0-inf were calculated to evaluate the bioequivalence.
Pharmacokinetic parameters were evaluated after the subjects took the test formulation and control formulation under the fasting status. The ratio of the geometric means of Cmax was 104.15%, with a CI of 98.20%-110.46%. The ratio of the geometric means of AUC0-t was 105.26%, with a CI of 99.80%-111.01%. The ratio of the geometric means of AUC0-inf was 105.37%, with a CI of 99.97%-111.06%. The pharmacokinetic parameters were also evaluated after the subjects took the reference formulation of the esomeprazole magnesium enteric-coated capsule after eating. The upper limit of the 95% confidence interval (CI) of the geometric mean ratio of the pharmacokinetic parameters of esomeprazole magnesium enteric-coated capsules in the postprandial state Cmax was -0.1689, and the point estimate was 0.9509 (0.80-1.25). The upper limit of the 95% confidence interval (CI) of the geometric mean ratio of the pharmacokinetic parameters of esomeprazole magnesium enteric-coated capsules in the postprandial state AUC0-t was -0.1015 (≤ 0), and the point estimate was 0.9003 (0.80-1.25). The upper limit of the 95% confidence interval (CI) of the geometric mean ratio of the pharmacokinetic parameters of esomeprazole magnesium enteric-coated capsules in the postprandial state AUC0-inf was -0.0593 (≤ 0), and the point estimate was 0.8453 (0.80-1.25). The results indicated that the two formulations were bioequivalent under both fasting and fed states.
The pharmacokinetic characteristics and bioequivalence of the two types of single-oral dose esomeprazole magnesium enteric-coated capsules were assessed. After oral administration, the 90% CI of the ratios of the geometric means of the primary pharmacokinetic parameters Cmax, AUC0-t, and AUC0-inf all fell within the acceptable limits of 80.00%-125.00%. In addition, although the meal extended the drug absorption, it had no impact on the Cmax, AUC0-t, or AUC0-inf of either of the formulations under the same status. Furthermore, no significant differences in safety issues were observed between treatment with the two formulations. Therefore, the two formulations of Eso enteric-coated capsules are considered bioequivalent.
The test formulation of the Eso enteric-coated capsule is equivalent to the reference formulation under both the fasting and fed states. Furthermore, no significant differences in safety issues were observed between treatments with the two formulations.