Winnonlin professional version 6

The serum concentrations vs. time data were analyzed with non-compartmental methods using WinNonlin Professional, Version 6.4 (Pharsight Corporation, NC, USA). The PK analysis used actual sample collection times. Samples below the LLOQ were set to zero before T_max and not detectable after T_max for the PK analysis. The PK parameters for paclitaxel included C_max, area under the curve (AUC)_0−t, AUC_0−∞, T_max, and T_1/2. Descriptive statistics were calculated for PK parameters, demographics, and safety variables and these were analyzed by t-test or analysis of variance (ANOVA). ANOVA also was used to compare the AUC and C_max, with factors fitted for the effect of sequence, subject within sequence, period, and treatment. The comparisons are presented in terms of the geometric least square means and the 90% confidence interval (CI). BE was established if the 90% CI of the treatment ratio was within the equivalence range of 0.8–1.25. T_max and T_1/2 were analyzed with a Wilcoxon rank test. All statistical tests were performed using SAS 9.1 Statistical Package, and P < 0.05 was considered statistically significant.

Pharmacokinetic analysis was performed using WinNonlin Professional, Version 6.4, software (Pharsight Corporation, Cary, NC, USA), and the plasma concentration vs. time data (pharmacokinetic parameters) were analyzed by using a noncompartmental method. The pharmacokinetic parameters for gefitinib included the maximum plasma concentration (C_max), area under the concentration–time curve from 0 h to the last time point (AUC_0−t), area under the concentration–time curve from 0 h to infinity (AUC_0−∞), time of maximum plasma concentration (T_max), and t_1/2. Descriptive statistics were calculated for the pharmacokinetic parameters; however, the demographic and safety variables were analyzed by the T-test or analysis of variance (ANOVA) model. CYP genotypes were compared by the chi-squared test. ANOVA was used to compare the AUC and C_max using the factors fitted for the effect of sequence, subject within sequence, period, and treatment. The comparison was presented in terms of the geometric least-square means, and the 90% CI. Bioequivalence was declared if the 90% CI of the treatment ratio was within the equivalence range of 0.8–1.25. T_max and t_1/2 were analyzed with the Wilcoxon signed-rank test. All statistical tests were performed by SAS 9.1 Statistical Package. P < 0.05 was considered statistically significant.