[Pharmacogenetics of immunosuppressants]

Abstract

Individualized drug therapy with immunosuppressants is an hot topic in transplantation. Therapeutic drug monitoring (TDM) is currently utilized to guide therapy, but toxic or subtherapeutic concentrations can only be identified after the drug is administered. Pharmacogenetics, by studying the relationship between a human genetic difference and drug response, holds great promises in optimizing immunosuppressive drug prescribing for solid organ transplantation.Nevertheless, a complete translation in the clinic has lagged behind,due to the overall complexity of the genetic approach, and the lack of sound evidence of identified genetic polymorphisms in ultimately explaining drug exposure. However, for tacrolimus it is likely that a genotype-based drug dosage can benefit patient outcome, while for cyclosporine data appear less convincing. Mycophenolic acid undergoes a complex metabolic pathway and various genes affecting drug disposition are under investigations, with promising results for some of them of being of value in aiding clinicians in decision making. Finally, for sirolimus and everolimus the lack of data and the absence of large prospective studies do not allow to draw any conclusion.