Evaluation of Bioequivalency and Pharmacokinetic Parameters for Two Formulations of Glimepiride 1-mg in Chinese Subjects

Abstract

Purpose

Glimepiride, an FDA-approved oral hypoglycemic drug, is a long-acting sulfonylurea (SU), used for treating type 2 diabetes. The study aimed to evaluate the bioequivalence and safety profiles of two different formulations of glimepiride 1 mg from two different manufactures in healthy Chinese subjects in the fasting and fed state in order to acquire adequate pharmacokinetic evidence for registration approval of the test formulation.

Patients and Methods

This study is an open-label, two-period, two-sequence, randomized, two-way crossover pharmacokinetic study in healthy Chinese subjects in the fasting and fed state. Seventy-two subjects were randomly assigned to the fasting group and the fed group (n=36 each). We collected blood samples, 24-h post drug administration. The plasma concentration of glimepiride was assessed using HPLC coupled with mass spectrometry. The following parameters were evaluated: AUC_0-inf, AUC_0-last, C_max, t_1⁄2, T_max, and λ_z. Safety was determined based on the occurrence of adverse events (AEs) and laboratory examinations (biochemistry, hematology, and urinalysis) throughout the entire study period.

Results

The geometric mean ratios (GMR) amongst the two glimepiride formulations for the primary pharmacokinetic parameters, ie, AUC_0-inf, AUC_0-last, and C_max as well as the corresponding 90% CIs, were all within the range of 80.00–125.00% in the fasting and fed state. The safety profile for both treatments was comparable.

Conclusion

PK analysis revealed that the test and reference formulations of glimepiride were bioequivalent and well tolerated in healthy Chinese subjects. Chinese Clinical Trials Registry identifier: CTR20171121.

Clinical Trial Registration Number

CTR20171121.

Keywords:

• glimepiride
• bioequivalence
• pharmacokinetics
• HPLC-MS/MS
• adverse event

Acknowledgments

We thank all of the healthy subjects for their participation in this study and the sponsor, Shandong Xinhua Pharmaceutical Co, Ltd for their financial support.

Data Sharing Statement

All available data is displayed in the article. No study protocol, statistical analysis plan and other information would be provided.

Ethics Approval and Informed Consent

This study was approved by the Drug Clinical Trial Ethics Committee of the Lanzhou University Second Hospital and conducted in accordance with the Declaration of Helsinki and was approved by an ethics committee. All subjects provided written informed consent.

Disclosure

Youwei Xu and Zhonghui Zheng are employees of Shandong Xinhua Pharmaceutical Company Limited. Shilin Chen is an employee of Chengdu Fanweixi Pharmaceutical Technology Company, Limited. The authors report no other conflicts of interest in this work.