Method for evaluating the human bioequivalence of acarbose based on pharmacodynamic parameters. Issue 10 (October 2020)

• Record Type: Journal Article
• Authors: Xu, Su-Mei; Xu, Yu-Ying; Yan, Juan; Zhang, Yi-Fei; Li, Dai; Li, Dan; Li, Xiao-Min; Guo, Jie; Xu, Ping-Sheng
• Is Part Of: Journal of international medical research. Volume 48:Issue 10(2020)
• Publication Date: 2020-10
• Subjects: Acarbose -- pharmacodynamics -- bioequivalence -- variability -- evaluation method -- pharmacokinetics -- crossover study; Medicine -- Periodicals; Pharmacology -- Periodicals; 610.5
• DOI: 10.1177/0300060520960317
• Languages: English
• ISSNs: 0300-0605

Abstract

Objective: To explore a method for evaluating the bioequivalence of acarbose based on pharmacodynamic parameters using a single-dose, randomized-sequence, three-way crossover study of acarbose test (T) and reference (R) formulations. Methods: Baseline-adjusted, pre-dose value deduction, and direct comparison methods were used to evaluate the geometric T/R ratios and 90% confidence intervals (CIs) of the ln-transformed pharmacodynamic parameters to identify the most suitable evaluation system. Twelve participants were randomly divided into three groups to receive treatment in the following sequences: TRR, RTR, and RRT, each including a 7-day washout period between treatment periods. The serum glucose concentration (baseline) was determined. Pharmacodynamic parameters, including the maximum reduction in serum glucose concentrations (ΔCSG, max ) and difference of the AUC of glucose between before and after acarbose exposure (ΔAUEC), were tested. Results: Using the direct comparison method, the geometric mean ratios of CSG, max, AUEC(0-2h), and AUEC(0-4h) were 94.13%, 97.82% and 99.76%, respectively. The 90% CIs of the geometric T/R ratios for CSG, max, AUEC(0-2h), and AUEC(0-4h) all fell between 80% and 125%. Conversely, ΔCSG, max and ΔAUEC(0-4h) were less reliable measures of acarbose bioequivalence. Conclusions: Pre-dose value deduction and direct comparison methods can be initially considered suitable for assessing acarbose bioequivalence.