Abstract
Background: Voglibose, an inhibitor of ${\alpha}$-glucosidase of the small intestine brush border, is used to treat type 2 diabetic patients. Bioequivalence test based on pharmacokinetic parameters is difficult because voglibose does not cross the enterocytes after ingestion. This study was conducted to establish bioequivalence of two formulations of 0.3-mg voglibose with pharmacodynamic endpoints. Methods: This study was an open, single-dose, randomized, 6-sequence, 3-period crossover design in healthy volunteers. In each period, subjects received placebo or three tablets of either test formulation or reference formulation with sucrose, with a 7-day washout period each dosing period. Serial blood samples were collected after each administration. The maximum concentrations of serum glucose and serum insulin ($C_{max}$(G) and $C_{max}$(I)) and the area under the serum concentration - time curve from dosing to 2 or 4 hours after dosing for serum glucose and insulin ($AUC_{0-2h}$(G), $AUC_{0-4h}$(G), $AUC_{0-2}$h(I) and $AUC_{0-4h}$(I), respectively) were determined by noncompartmental analysis. Formulation-related differences were tested in accordance with the Korean regulatory bioequivalence criteria. Results: A total of 54 subjects completed study in accordance with protocol. The geometric mean ratios (GMRs) of the test formulation to the reference formulation for Cmax(G), $AUC_{0-2h}$(G), $AUC_{0-4h}$(G), $C_{max}$(I), $AUC_{0-2h}$(I) and $AUC_{0-4h}$(I) were 0.945, 1.014, 0.995, 0.937, 0.985 and 0.983, respectively and the 90 % confidence intervals (CIs) of corresponding values were 0.985-1.026, 0.991-1.038, 0.977-1.014, 0.830-1.057, 0.901-1.078 and 0.911-1.014, respectively. Conclusion: This single-dose study found that two formulations of 0.3-mg voglibose did not meet the regulatory criteria for bioequivalence in these healthy volunteers.
