Pharmacodynamic assessment
For pharmacodynamic analysis, serial blood samples were collected during oral glucose tolerance test (OGTT); 0 (pre-OGTT), 0.25, 0.5, 1, 1.5, 2 and 3 hours after administration of glucose (75 g) for measurement of serum glucose and plasma insulin level. OGTT was conducted at the day before first study drug administration at period 1 (baseline) and 2 hours after study drug administration at sixth day of each period.
Individual steady-state serum glucose and plasma insulin parameters of each period were calculated by non-compartmental methods using Phoenix WinNonlin® software. Maximum concentration of serum glucose and plasma insulin at steady-state (Gmax,ss, Emax,ss) were directly derived from observed data. Area under the serum glucose and plasma insulin concentration-time curve during a dosing interval at steady-state (AUGCτ,ss, AUECτ,ss) were calculated by the linear trapezoidal method.
Plasma concentrations of insulin were analyzed with immunoradiometric assay (IRMA) method (gamma counter: Dream Gamma-10, Shin Jin, Republic of Korea). Serum concentrations of glucose were analyzed with glucose hexokinase assay method (automatic chemical analyzer: TBA-FX8, Toshiba, Japan).