title: Longitudinal Pharmacokinetics of Tacrolimus in Elderly Compared With Younger Recipients in the First 6 Months After Renal Transplantation.
abstract: Elderly (Eld) (≥60 years) recipients are receiving renal transplants more frequently. The pharmacokinetics (PK) studies of immunosuppressive drugs in healthy volunteers, rarely, include old patients.
  
  
  
  We studied 208 12-hour tacrolimus (TAC) PK (0, 20, 40, 60, 90, 120, 180, 240, 360, 480, 600, 720 min) in 44 Eld (65 ± 3 years) and compared the results with 31 younger controls (Ctrl) (35 ± 6 years) recipients, taking oral TAC/mycophenolate sodium (MPS)/prednisone, at 4 different timepoints: PK1 (8 ± 2 days; n = 72), PK2 (31 ± 4 days; n = 61), PK3 (63 ± 6 days; n = 44), and PK4 (185 ± 10 days; n = 31). Tacrolimus PK was measured by ultraperformance liquid chromatography coupled to a mass spectrometer repetition and noncompartmental PKs were analyzed using Phoenix WinNonlin.
  
  
  
  Mean TAC dose was lower in the Eld group than in Ctrl ones throughout timepoints either by total daily dose or adjusted (Adj) per body weight. Mean TAC trough level (Cmin), used to adjust daily dose, was not different between the 2 groups in all timepoints. AdjCmax and AdjTAC-area under the curve at dosing interval were both higher in the Eld compared to the Ctrl group in PKs1, 3, and 4. Estimated total body clearance normalized by dose and weight was lower in the Eld group compared with the Ctrl in all PKs and statistically lower at PKs 1 and 3. Similar to younger recipients TAC trough level has also a high correlation (R = 0.76) with area under the curve at dosing interval.
  
  
  
  These data indicate that Eld recipients have a lower TAC clearance and therefore need a lower TAC dose than younger recipients.
authors.affiliation: 1 Renal Transplantation Service, University of São Paulo School of Medicine, São Paulo, Brazil. 2 Division of Central Laboratory, University of São Paulo School of Medicine, São Paulo, Brazil. 3 Department of Geriatrics, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Elias
authors.initials: E
authors.lastname: David-Neto
authors.forename: Paschoalina
authors.initials: P
authors.lastname: Romano
authors.forename: Ana Heloisa
authors.initials: AH
authors.lastname: Kamada Triboni
authors.forename: Fernanda
authors.initials: F
authors.lastname: Ramos
authors.forename: Fabiana
authors.initials: F
authors.lastname: Agena
authors.forename: Persio
authors.initials: P
authors.lastname: Almeida Rezende Ebner
authors.forename: Marcelo
authors.initials: M
authors.lastname: Altona
authors.forename: Nelson Zocoler
authors.initials: NZ
authors.lastname: Galante
authors.forename: Francine
authors.initials: F
authors.lastname: Brambate Carvalhinho Lemos
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001938:Brazil; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000009:adverse effects; D008137:Longitudinal Studies; D008297:Male; D013058:Mass Spectrometry; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016559:Tacrolimus