Biomarkers in transplantation medicine: Prediction of pharmacodynamic drug effects

Conventional therapeutic drug monitoring based on measuring of blood concentrations (pharmacokinetic) is important in the clinical management of immunosuppressive therapy in transplantation medicine. Since rejection or infection occurs at irregular drug concentrations, immunosuppressive drug therapy is often empiric and prophylactic in nature. In addition, blood immunosuppressant levels are only indirect predictors of the pharmacologic effects on immune cells (pharmacodynamic) because, due to the genetic heterogeneity, the immune systems of the transplant recipients are not equally sensitive to drug effects. Therefore, therapeutic drug monitoring requires the application of reliable and effective methods to study the pharmacodynamic variability by direct measurements of drugs effects on immune cell functions. Against this background we developed assays which are based on whole blood, flow cytometry and biomarkers of diverse functions of T cells and of dendritic cell subsets. These biomarker assays allow us to differentiate between synergistic and antagonistic pharmacodynamic effects of an immunosuppressive drug combination therapy in vitro and to predict the pharmacodynamic drug effects in heart-transplanted recipients. Such a pharmacodynamic drug monitoring based on biomarkers may offer the opportunity to complete conventional therapeutic drug monitoring and, therefore, to tailor immunosuppressive therapy more individually.