PK/PD Studies

One of the challenges of early drug development is to provide bona fide proof-of-concept of efficacy in validated animal models of disease. Many of these models are based on behavioral endpoints, which are challenging to interpret. Furthermore, lead molecules often present challenges in terms of their bioavailability at the target tissue. Correlating pharmacokinetic data (PK) with pharmacodynamic outcomes (PD) has become a gold standard to demonstrate pharmacological activity. However, depending on the endpoint and the actual tissue distribution, these correlations are not always consistent. In more difficult cases, Cytochem’s toolbox may offer interesting solutions.

Combining labeled compounds with Cytochem’s whole-body autoradiography provides a much more precise method to ascertain whether or not the compound actually reached the intended site of action. Alternatively, using genes as biomarkers of drug activity may also provide useful insight in the absence of behavioral effects. Furthermore, using adjacent whole-body sections, biomarker gene expression profiles can also be overlaid on tissue distribution autoradiograms of labeled compound to establish the PK/PD relationship.