Coadministration of lapatinib increases exposure to docetaxel but not doxorubicin in the small intestine of mice.

ABSTRACT: Combination therapy is increasingly being utilized for the treatment of metastatic breast cancer. However, coadministration of drugs, particularly agents that are substrates for or inhibitors of p-glycoprotein, can result in increased tissue toxicity. Unfortunately, determination of levels of chemotherapeutics in human tissues is challenging, and plasma drug concentrations are not always indicative of tissue toxicokinetics or toxicodynamics, especially when tissue penetration is altered. The aim of the present work was to determine whether concomitant administration of compounds currently being combined in clinical trials for metastatic breast cancer treatment alters plasma and tissue pharmacokinetics in mice if both agents are p-glycoprotein substrates and/or inhibitors. Accordingly, we i

SUBMITTER: Hudachek SF 

PROVIDER: S-EPMC4694043 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature