Translational pharmacokinetic/pharmacodynamic analysis in cancer pharmacology: a tool to maximize the value of antitumor efficacy from tumor bearing mice

Abstract

Translational pharmacokinetic/pharmacodynamic (PK/PD) analysis is becoming an increasingly important tool for the identification and selection of new anticancer agents. There are two important elements of effectively using PK/PD analysis to translate preclinical antitumor efficacy from tumor bearing mice (xenografts and allografts) to cancer patients. These two sometimes overlapping elements are termed translation 'WITHIN' and 'ACROSS' species. Translating 'WITHIN' species refers to the quantitative characterization of drug action and disease behavior within tumor bearing mice using PK/PD modeling in order to use this information to make predictions of drug response in humans. Translating 'ACROSS' species refers to use of PK/PD modeling to quantify species similarities and differences in drug response in order to understand the clinical relevance of preclinical efficacy data.