LAUSR

2525Background: The aim of this analysis was to develop a PPK model for IV trastuzumab (Herceptin), to assess the impact of patient covariates on PK, and perform simulations to support dosing recommendations. Methods: Serum trastuzumab concentration data (26,040 samples) from 1582 patients with metastatic breast cancer (MBC), early breast cancer (EBC), advanced gastric cancer (AGC) or other tumor types, and 6 healthy volunteers in 18 Phase I, II, and III trials were analyzed using nonlinear mixed-effects modeling (NONMEM). Monte Carlo simulations were performed using the NONMEM PK parameter estimates (with variability) to inform dosing recommendations. Results: A two-compartment model with parallel linear and nonlinear elimination best described the data. Significant covariates (P < 0.001) influencing linear CL were baseline weight, SGOT, albumin, primary tumor type, and presence of liver metastases. MBC had similar PK parameters as EBC, with lower distributions of Cmin,ss in MBC explained by covariates. ...