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).