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

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) 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, AUEC, and AUEC were 94.13%, 97.82% and 99.76%, respectively. The 90% CIs of the geometric T/R ratios for C, AUEC and AUEC all fell between 80% and 125%. Conversely, ΔC and ΔAUEC 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.