title: Longitudinal Pharmacokinetics of Everolimus When Combined With Low-level of Tacrolimus in Elderly Renal Transplant Recipients.
abstract: Although the proportion of elderly patients among renal transplant recipients has increased, pharmacokinetic (PK) studies of immunosuppressants rarely include older patients.
  
  
  
  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 (Ctrough, 3-8 ng/mL), prednisone, and tacrolimus (TCL) (target Ctrough, 2-5 ng/mL).
  
  
  
  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 timepoints for mean EVL daily dose (data shown as PK3) (3.5 ± 1.3 mg/d), Ctrough (4.7 ± 2.5 ng/mL), AUC0-12h (106 ± 51 ng/h per mL), Caverage (8.8 ± 4.2 ng/mL), Cmax (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-Ctrough showed a very high correlation (r = 0.849) with AUC0-12h.
  
  
  
  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.
authors: 1 Kidney Transplant Service, University of São Paulo School of Medicine, São Paulo, Brazil. 2 Central Laboratory, Division of Pathology and Geriatric Service, University of São Paulo School of Medicine, São Paulo, Brazil. 3 Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil.
authors: Elias
authors: E
authors: David-Neto
authors: Fabiana
authors: F
authors: Agena
authors: Fernanda
authors: F
authors: Ramos
authors: Ana Heloisa Kamada
authors: AHK
authors: Triboni
authors: Paschoalina
authors: P
authors: Romano
authors: Persio
authors: P
authors: de Almeida Rezende Ebner
authors: Venceslau
authors: V
authors: Coelho
authors: Nelson Zocoler
authors: NZ
authors: Galante
authors: Francine Brambate Carvalhinho
authors: FBC
authors: Lemos
mesh_terms: D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D001938:Brazil; D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008137:Longitudinal Studies; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D016559:Tacrolimus