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-hour everolimus (EVL) PK in 16 elderly renal transplant recipients (all whites; 10 men; mean age, 64 2 years (61-71 years), in 4 separate timepoints (at 7, 30, 60, and 150 days) after EVL introduction, corresponding to a mean postrenal transplantation day: PK1 (43 4 days), PK2 (65 +/- 7 days), PK3 (106 +/- 17 days), and PK4 (206 +/- 40 days). Patients received EVL (target trough level (C-trough, 3-8 ng/mL), prednisone, and tacrolimus (TCL) (target C-trough, 2-5 ng/mL). Results Mean TCL-C-trough 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 timepoints for mean EVL daily dose (data shown as PK3) (3.5 +/- 1.3 mg/d), C-trough (4.7 +/- 2.5 ng/mL), AUC(0-12h) (106 +/- 51 ng/h per mL), C-average (8.8 +/- 4.2 ng/mL), C-max (19.2 +/- 9.7 ng/mL), apparent Half-life (11.7 +/- 4.2 hours), estimated total body clearance (0.39 +/- 0.27 L/h), or fluctuation (166 +/- 65%). Also, none of those PK parameters differed statistically when adjusted for body weight. EVL-C-trough showed a very high correlation (r(2) = 0.849) with AUC(0-12h). 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.