Calculated Log D Is Inversely Correlated With Select Camptothecin Clearance and Efficacy in Colon Cancer Xenografts.

ABSTRACT: Quantitative structure-property relationships are often derived to identify molecular determinants of drug potency and facilitate drug design. However, compound activity is typically based on in vitro bioassays, and the influence of physicochemical properties on pharmacokinetic/pharmacodynamic (PK/PD) behavior is not considered. Here, we integrate PK/PD and quantitative structure-property relationship modeling to evaluate the role of lipophilicity in camptothecin antitumor responses in colon cancer xenografts. Drug exposure and tumor growth profiles for 5 camptothecins were extracted from the literature. A PK/PD model with time-dependent transduction was developed, which characterized PK and tumor growth inhibition. Correlations between drug lipophilicity (log D), in vitro potency (IC50),

SUBMITTER: Nanavati C 

PROVIDER: S-EPMC4813326 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature