Case Control Study
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World J Clin Cases. Nov 26, 2020; 8(22): 5518-5528
Published online Nov 26, 2020. doi: 10.12998/wjcc.v8.i22.5518
Bioequivalence of two esomeprazole magnesium enteric-coated formulations in healthy Chinese subjects
Zheng-Zhi Liu, Qing Ren, Yan-Nan Zhou, Hai-Miao Yang
Zheng-Zhi Liu, Qing Ren, Yan-Nan Zhou, Hai-Miao Yang, Phase I Clinical Trial Laboratory, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, China
Author contributions: Liu ZZ, Yang HM, contributed equally to this work; Liu ZZ, Yang HM designed the research study; Liu ZZ, Ren Q, Zhou YN performed the research; Liu ZZ analyzed the data and wrote the manuscript; all authors have read and approved the final manuscript.
Institutional review board statement: The study protocol was approved by the Ethics Committee of Changchun University of Chinese Medicine Affiliated Hospital.
Informed consent statement: All participates provided written informed consent prior to study inclusion.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hai-Miao Yang, MSc, Chief Doctor, Phase I Clinical Trial Laboratory, Affiliated Hospital of Changchun University of Chinese Medicine, No. 1478 Gongnong Road, Changchun 130021, Jilin Province, China. 315597629@qq.com
Received: June 5, 2020
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
Abstract
BACKGROUND

The pharmacokinetics and bioequivalence of esomeprazole in healthy Chinese subjects and the effects of food on the pharmacokinetics have not been well studied.

AIM

To evaluate the pharmacokinetic characteristics of esomeprazole magnesium (Eso) enteric- coated capsule in the healthy subjects in China and the bioequivalence of the two formulations.

METHODS

This study was conducted in the Phase I Clinical Trial Unit of the Affiliated Hospital of Changchun University of Chinese Medicine. A total of 64 healthy subjects were enrolled in the study. Thirty-two subjects fasted or fed, 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 performed 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 (AUC)0-t, and AUC0-inf were calculated to evaluate the bioequivalence.

RESULTS

Pharmacokinetic parameters were evaluated after subjects took the test formulation and control formulation under fasting status. The ratio of geometric means of Cmax was 104.15%, with a confidence interval (CI) of 98.20-110.46%. The ratio of geometric means of AUC0-t was 105.26%, with a CI of 99.80-111.01%. The ratio of geometric means of AUC0-inf was 105.37%, with a CI of 99.97-111.06%. The pharmacokinetic parameters were also evaluated after subjects took the reference formulation of Eso enteric-coated capsule after eating. The upper limit of 95% CI of the geometric mean ratio of pharmacokinetic parameters of Eso 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 95% CI of the geometric mean ratio of pharmacokinetic parameters of Eso 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 95% CI of the geometric mean ratio of pharmacokinetic parameters of Eso 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.

CONCLUSION

The two types of esomeprazole tablets were bioequivalent under both fasting and fed states, and both were generally well tolerated.

Keywords: Esomeprazole; Proton pump inhibitor; Bioequivalence; Pharmacodynamics; Gastroesophageal reflux disease

Core Tip: The pharmacokinetic characteristics and bioequivalence of two types of single oral dose esomeprazole magnesium (Eso) enteric-coated capsules were assessed. The 90%CI of the ratios of geometric means of the primary pharmacokinetic parameters all fell within the acceptable limits of 80.00%-125.00%. Although meal was able to extend drug absorption, it had no impact on Cmax, AUC0-t, or AUC0-inf, of either of the two formulations under the same status. Furthermore, no significant differences in safety issues were observed between the two formulations. Therefore, the two formulations of Eso enteric-coated capsules are considered bioequivalence.