Population Pharmacokinetics and Pharmacogenetics of Everolimus in Renal Transplant Patients

Background and Objective Everolimus is a novel macrolide immunosuppressant used in the prevention of acute and chronic rejection of solid organ transplants. Everolimus is being actively investigated worldwide as a non-nephrotoxic alternative for calcineurin inhibitors. Its highly variable pharmacokinetics and narrow therapeutic window make it difficult to maintain an adequate exposure to prevent serious adverse effects. The primary objective of this study was to improve prediction of everolimus systemic exposure in renal transplant patients by describing the pharmacokinetics of everolimus and identifying the influence of demographic factors and a selection of polymorphisms in genes coding for ABCB1, CYP3A5, CYP2C8 and PXR. The secondary objective of this study was to develop a limited sampling strategy to enable prediction of everolimus exposure in an efficient way and to compare it with the widely used trough blood concentration (Ctrough) monitoring.