Pharmacokinetic considerations for new targeted therapies

Abstract

Targeted therapies are increasingly being incorporated into standard treatment regimens for cancer. Tyrosine kinase inhibitors represent one class of targeted agents, with eight drugs receiving approval for the treatment of cancer in recent years. Although they hold the promise of being more effective and less toxic to normal cells than conventional cytotoxic chemotherapy, tyrosine kinase inhibitors are associated with different adverse effects, sometimes severe, as well as wide pharmacokinetic variability. Thus, a “therapeutic window” may exist for these agents.

Figure 1

Scheme for the involvement of solute carriers (SLC), ATP-binding cassette transporters (ABC), and drug-metabolizing enzymes (CYP) in the absorption and disposition of orally administered tyrosine kinase inhibitors. RTK, receptor tyrosine kinase.