Pharmacokinetic Parameters and Statistical Analysis
Non-compartmental model was carried out to calculate the pharmacokinetic
parameters using Phoenix WinNonLin (Pharsight Corporation, version 8.1,
Mountain View, CA). The pharmacokinetic parameters were as follows: the
peak plasma concentration (Cmax) and the time to reach
Cmax (Tmax) were obtained directly from
the concentration-time profile. The areas under the plasma
concentration-time curve (AUC0-t or
AUC0-∞) were calculated from time 0 to the end time of
the concentration-time profile or infinity. The first-order terminal
rate constant (k el) was estimated using linear
regression of the terminal log-linear decay phase. Statistical analysis
was executed using SAS software and Cmax,
AUC0-t, and AUC0-∞ were compared between
two formulations using 1-way analysis of variance (ANOVA) on
log-transformed pharmacokinetic values. The p value of < 0.05
was considered statistically significant. According to FDA guidance, the
T and R were considered bioequivalent if the 90% confidence interval
(CI) for the ratio of the geometric least-squares means was within the
equivalence limits (80.0-125.0%) for the primary end points
Cmax, AUC0-t, and AUC0-∞[9]..