Pharmacokinetics of Tacrolimus (TAC) in Elderly Compared to Young Recipients in the First Year After Renal Transplantation. Data from the NEverOLd Trial

E. David-Neto,¹ P. Romano,² A. Triboni,¹ F. Agena,¹ P. Ebner,² F. Ramos,¹ N. Galante,¹ F. Lemos.¹

¹Renal Transplantation Service, Hospital das Clinicas –
University of São Paulo School of Medicine, Sao Paulo, Brazil
²Division of Central Laboratory, Hospital das Clinicas –
University of São Paulo School of Medicine, Sao Paulo, Brazil.

Meeting: 2015 American Transplant Congress

Abstract number: D118

Keywords: Elderly patients, Immunosuppression, Kidney transplantation

Session Information

Session Name: Poster Session D: Kidney Immunosuppression: Drug Minimization

Session Type: Poster Session

Date: Tuesday, May 5, 2015

Session Time: 5:30pm-6:30pm

Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Elderly (≥60years) recipients are nowadays receiving renal transplants more frequently. The pharmacokinetics studies (PK) of immunosuppressive drugs in healthy volunteers, rarely, if ever, include old patients. We studied 245, 12-hour Tacrolimus (TAC) PK (0,20,40,60,90,120,180,240,360,480,600,720 min.) in 44 elderly (Eld) (63±1year; range 61-71years) and compared the results with 31 younger (Yng) (41±5y) recipients, taking oral Tacrolimus (TAC)/Mycophenolate Sodium (MPS)/prednisone, at 5 different time-points: PK1 (8±2days; n=72); PK2 (31±4d; n=61); PK3 (63±6d; n=44) and PK4 (93±5days; n=37), PK5 (185±10days; n=31). TAC PK was measured by Ultra Performance Liquid Chromatography coupled to a mass spectrometer repetition (UPLC/MS/MS) and PKs were analyzed using Phoenix WinNonlin. Mean TAC dose was much lower in the Eld group than in Yng ones throughout time points either by total daily dose or adjusted per body weight (adj) (e.g. PK1: 0.08±0.03 vs 0.12±0.03 and PK5: 0.03±0.01 vs 0.06±0.04 mg/kg/d, p=0.01). Mean TAC through level (Cmin) was not different between the 2 groups in any time-points (e.g. PK1: 6.1±3.1 vs 5.7±2.2 and PK5: 4.12±2.4 vs 3.5±1.8 ng/ml, p=0.44). Adjusted Cmax was higher in the Eld compared to the Yng group in all PKs (458±261 vs 346±223 ng*kg/ml/mg, p=0.000) and Tmax in Eld occurred in a later time compared to Yng recipients (1.68±1.35 vs 1.37±0.71h, p=0.04). AdjTAC-AUC0-720 was higher in the Eld group in all time-points (2638±1689 vs 1836±1209 hr*kg*ng/ml/mg, p=0.000) as well as average TAC concentration (Cavg) (12.0±5.5 vs 11.2±5.9 ng/mL, p=0.038). Total body clearance (Clss_F) normalized by dose and weight was lower in the Eld group compared to the Yng (0.54.±0.42 vs 0.74±0.42 L/kg/h, p=0.000) These data indicate that elderly patients need a lower adjusted TAC dose than Yng recipients and have a good oral TAC availability. Elderly recipients also show a low TAC clearance. The results of good availability and low clearance may lead to a higher exposure if the dose is not corrected by frequent monitoring.

To cite this abstract in AMA style:

David-Neto E, Romano P, Triboni A, Agena F, Ebner P, Ramos F, Galante N, Lemos F. Pharmacokinetics of Tacrolimus (TAC) in Elderly Compared to Young Recipients in the First Year After Renal Transplantation. Data from the NEverOLd Trial [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/pharmacokinetics-of-tacrolimus-tac-in-elderly-compared-to-young-recipients-in-the-first-year-after-renal-transplantation-data-from-the-neverold-trial/. Accessed May 11, 2025.

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