Longitudinal Pharmacokinetics of Everolimus when Combined with Low-level of Tacrolimus in Elderly Renal Transplant Recipients.

Background: Although the proportion of elderly patients among renal transplant recipients has increased, pharmacokinetic (PK) studies of immunosuppressants rarely include older patients. Methods: We studied 12-hours everolimus (EVL) PK in 16 elderly renal transplant recipients (all caucasians; 10 males; mean age, 64+/-2 years, (61-71y), in 4 separate time-points (at 7, 30, 60 and 150 days) after EVL introduction, corresponding to a mean post renal-transplantation day: PK1 (43+/-4days), PK2 (65+/-7 days), PK3 (106+/-17 days) and PK4 (206+/-40 days). Patients received EVL (target trough level (Ctrough: 3-8 ng/mL), prednisone and tacrolimus (TCL) (target Ctrough: 2-5 ng/mL). Results: Mean TCL- Ctrough was 7.2+/-3.8, 4.9+/-2.2, 4.9+/-2.2, and 4.5+/-1.2 ng/mL at PK1, PK2, PK3 and PK4, respectively. There were no differences among time-points for mean EVL daily dose (data shown as PK3) (3.5+/-1.3 mg/day), Ctrough (4.7+/-2.5 ng/mL), AUC0-12h (106+/-51 ng*h/mL), Caverage (8.8+/-4.2 ng/mL), Cmax (19.2+/-9.7ng/mL), apparent Half-life (11.7+/-4.2 hours), estimated total body Clearance (0.39+/-0.27 L/hour), or Fluctuation (166+/-65%). Also, none of those PK parameters differed statistically when adjusted for body weight. EVL-Ctrough showed a very high correlation (r2 =0.849) with AUC0-12h. Conclusions: Our data indicate that elderly renal transplant recipients starting EVL 1 month after transplantation along with a steady-state TCL level, present stable EVL-PK parameters without significant changes in dose or exposure during the first 6 months after renal transplantation. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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