Intratumoral modeling of gefitinib pharmacokinetics and pharmacodynamics in an orthotopic mouse model of glioblastoma.

ABSTRACT: Like many solid tumors, glioblastomas are characterized by intratumoral biologic heterogeneity that may contribute to a variable distribution of drugs and their associated pharmacodynamic responses, such that the standard pharmacokinetic approaches based on analysis of whole-tumor homogenates may be inaccurate. To address this aspect of tumor pharmacology, we analyzed intratumoral pharmacokinetic/pharmacodynamic characteristics of the EGFR inhibitor gefitinib in mice with intracerebral tumors and developed corresponding mathematical models. Following a single oral dose of gefitinib (50 or 150 mg/kg), tumors were processed at selected times according to a novel brain tumor sectioning protocol that generated serial samples to measure gefitinib concentrations, phosphorylated extracellular sig

SUBMITTER: Sharma J 

PROVIDER: S-EPMC3755354 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature