Method for evaluating the human bioequivalence of acarbose based on pharmacodynamic parameters

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 (ΔC SG,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 C SG,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 C SG,max , AUEC (0-2h), and AUEC (0-4h) all fell between 80% and 125%. Conversely, ΔC SG,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.