Affiliation:
1. Pharmaceutical and Biomedical Sciences University of Georgia 240 W. Green St Athens GA 30602 USA
2. Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center 1901 East Rd. Houston TX 77054 USA
3. Institute of Bioinformatics University of Georgia 20 Green St. Athens GA 30602 USA
Abstract
AbstractTissue endothelial cells express ABC‐transporter enzymes that change the concentration of small molecules within different tissue compartments. These “blood‐tissue barriers” have been shown to directly affect the efficacy and toxicity of anticancer, antimicrobial, psychiatric, and anti‐epileptic drugs. Currently this phenomenon is best studied for the blood‐brain barrier, but remains enigmatic for most other tissues. In addition, canonical pharmacokinetic theory specifically assumes an equal concentration of free drug within all tissue compartments. Inspired by Lipinski's “rule of 5,” we here clarify current knowledge on drug–tissue distribution by: 1) curating the in‐vivo literature on 73 drugs across 23 tissues and 2) developing two graphical web‐based applications to visually describe and interpret data. These curated in‐vivo dataset and visualization tools enabled us to achieve new insights into the logic of the barrier‐tissue organization and showed remarkable correspondence to whole‐body imaging of radiolabeled molecules.
Subject
Organic Chemistry,Molecular Biology,Molecular Medicine,Biochemistry