Pharmacodynamics of immunosuppressive drugs

The inability to measure the effects of immunosuppressive drugs on immune cells in vivo has always severely limited preclinical drug development, the design and interpretation of clinical trials and the optimal clinical use of this drug class in transplantation. Now, new technologies using microliter samples of whole blood and exploiting the specificity, sensitivity and versatility of flow cytometry have been developed. These novel techniques not only are illuminating the ‘black box’ that has obscured the pharmacodynamic effects of immunosuppressants but also are uncovering new mechanisms of action of these drugs. Pharmacodynamic assays measure biologically relevant events in vivo, since changes in lymphocyte functions in blood collected from immunosuppressed graft recipients faithfully reflect histopathologic events within allograft tissue.