Drug Design, Development and Therapy (Jul 2020)

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

  • Ju G,
  • Yan K,
  • Xu Y,
  • Chen S,
  • Zheng Z,
  • Qiu W

Journal volume & issue
Vol. Volume 14
pp. 2637 – 2644

Abstract

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Gehang Ju,1 Keyu Yan,1 Youwei Xu,2 Shilin Chen,3 Zhonghui Zheng,2 Wen Qiu4 1School of Pharmacy Lanzhou University, Lanzhou University, Lanzhou, People’s Republic of China; 2Research Institute, Shandong Xinhua Pharmaceutical Company Limited, Shandong, People’s Republic of China; 3The Department of Analysis, Chengdu Fanweixi Pharmaceutical Technology Company, Limited, Chengdu, People’s Republic of China; 4Phase I Clinical Unit, Lanzhou University Second Hospital, Lanzhou, People’s Republic of ChinaCorrespondence: Wen Qiu Tel/ Fax +86-931-8487117Email [email protected]: 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: AUC0-inf, AUC0-last, Cmax, t1⁄ 2, Tmax, and λz. 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, AUC0-inf, AUC0-last, and Cmax 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

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