Abstract
Conventional therapeutic drug monitoring based onmeasuring of blood concentrations (pharmacokinetic) isimportant in the clinical management of immunosuppressivetherapy in transplantation medicine. Since rejectionor infection occurs at irregular drug concentrations,immunosuppressive drug therapy is often empiricand prophylactic in nature. In addition, blood immunosuppressantlevels are only indirect predictors of thepharmacologic effects on immune cells (pharmacodynamic)because, due to the genetic heterogeneity, theimmune systems of the transplant recipients are notequally sensitive to drug effects. Therefore, therapeuticdrug monitoring requires the application of reliable andeffective methods to study the pharmacodynamic variabilityby direct measurements of drugs effects on immunecell functions. Against this background we developedassays which are based on whole blood, flow cytometryand biomarkers of diverse functions of T cellsand of dendritic cell subsets. These biomarker assaysallow us to differentiate between synergistic and antagonisticpharmacodynamic effects of an immunosuppressivedrug combination therapy in vitro and to predict thepharmacodynamic drug effects in heart-transplanted recipients.Such a pharmacodynamic drug monitoringbased on biomarkers may offer the opportunity to completeconventional therapeutic drug monitoring and,therefore, to tailor immunosuppressive therapy moreindividually.
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