Population pharmacokinetic and covariate analyses of intravenous trastuzumab (Herceptin^®), a HER2-targeted monoclonal antibody, in patients with a variety of solid tumors.

ABSTRACT:

Purpose

The aim of the study was to characterize the population pharmacokinetics (PK) of the intravenous formulation of trastuzumab, assess the impact of patient and pathological covariates on trastuzumab PK, and perform simulations to support dosing recommendations in special situations.

Methods

Serum trastuzumab concentrations were obtained from 1582 patients with metastatic breast cancer (MBC), early breast cancer (EBC), advanced gastric cancer (AGC), or other tumor types/healthy volunteers in 18 phase I, II, and III trials and analyzed by nonlinear mixed-effects modeling.

Results

A two-compartment model with parallel linear and nonlinear elimination best described the data. During treatment, linear clearance (CL) dominated, resulting in a total CL of 0.173-0.337 L

SUBMITTER: Quartino AL 

PROVIDER: S-EPMC6394489 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature