Immunosuppressive drug monitoring - what to use in clinical practice today to improve renal graft outcome

Abstract

Therapeutic drug monitoring (TDM) of immunosuppressive therapy is becoming an increasingly complex matter as the number of compounds and their respective combinations are continuously expanding. Unfortunately, in clinical practice, monitoring predose trough blood concentrations is often not sufficient for guiding optimal long-term dosing of these drugs. The excellent short-term results obtained nowadays in renal transplantation confer a misleading feeling of safety despite the fact that long-term results have not substantially improved, definitely not to a point where longer graft survival could counteract the increasing need for transplant organs and less toxicity and side-effects could ameliorate patient survival. It is therefore a challenging task to try to tailor immunosuppressive drug therapy to the individual patient profile and this in a time-dependent manner. For the majority of currently used immunosuppressive drugs, measurement of total drug exposure by determination of the dose-interval area under the concentration curve (AUC) seems to provide more useful information for clinicians in terms of concentration-exposure and exposure-response as well as reproducibility. To simplify this laborious way of measuring drug exposure, several validated abbreviated AUC profiles, accurately predicting the dose-interval AUC, have been put forward. Together with an increasing knowledge of the time-related pharmacokinetic behaviour of immunosuppressive drug and their metabolites, studies are focusing on how to apply abbreviated AUC sampling methods in clinical transplantation, taking into account the numerous factors affecting drug pharmacokinetics. Eventually, TDM using abbreviated AUC profiles has to be prospectively tested against classic methods of drug monitoring in terms of cost-effectiveness, feasibility and clinical relevance with the ultimate goal of improving patient and graft survival.