PK analysis was performed with the data of all subjects using the software Phoenix WinNonlin® version 8.0 (Pharsight, St. Louis, MO, USA) and SAS version 9.3 (SAS Institute, Cary, NC, USA). All concentration values that were below the limit of quantification were considered as zero. Missing values were not included in the PK analysis. The estimated Cmax, Tmax, T1/2, and the elimination rate constant (Lambda_z). The area under the curve of plasma concentration versus time was also calculated from time zero to the AUClast.
The area under the curve of concentration versus AUCinf was calculated using the linear trapezoidal rule, and the extrapolated AUC percentage of total AUC was calculated as
Total CL was calculated as the total dose (mg) divided by AUCinf (CL), and the Vd based on the terminal was calculated as
When AUCext was greater than 20%, AUCinf and its associated parameters (T1/2, CL, and Vd) were set as missing, and AUClast was reported. A non-compartmental method (Model 200 of Phoenix WinNonlin® 5.2, Pharsight, St. Louis, MO, USA) was used to estimate the PK parameters of T-DM1, total trastuzumab, and DM1.
The area under the curve of concentration versus AUCinf was calculated using the linear trapezoidal rule, and the extrapolated AUC percentage of total AUC was calculated as
Total CL was calculated as the total dose (mg) divided by AUCinf (CL), and the Vd based on the terminal was calculated as
When AUCext was greater than 20%, AUCinf and its associated parameters (T1/2, CL, and Vd) were set as missing, and AUClast was reported. A non-compartmental method (Model 200 of Phoenix WinNonlin® 5.2, Pharsight, St. Louis, MO, USA) was used to estimate the PK parameters of T-DM1, total trastuzumab, and DM1.