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]..