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

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

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

Meeting: 2015 American Transplant Congress

Abstract number: D148

Keywords: Immunosuppression, Kidney transplantation, Pharmacokinetics

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 mycophenolic acid (MPA) PK (0,20,40,60,90,120,180,240,360,480,600,720 min.) in 44 elderly (Eld) (63±1y; range 61-71years) and compared with 31 younger (Yng) (41±5y) recipients taking oral Mycophenolate Sodium (MPS)/Tacrolimus (TAC)/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). MPA 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 through levels at each time-points were 7.2±4.9; 7.2±4.4; 7.1±4.1; 5.1±2.3 and 4.3±2.7ng/mL and did not differ between groups. Mean MPS daily dose did not differ between groups throughout time-points either by total daily dose or dose adjusted per body weight (adj) with exception of PK5 where Yng received a higher adjusted dose (10.5±3.0 vs 8.0±2.5mg/k/d, p=0.017). Mean MPA through level (Cmin) was lower in Eld in all time points (p=0.004). Also, MPA-AUC0-720min was lower (p=0.000) in the Eld group in all time-points (e.g. PK1:45±55 vs 62±54 and PK5: 33±21 vs 58±34 ug*hr/ml, p=0.000). Average MPA concentration (Cavg) was lower in the Eld group (3.67±3.09 vs 5.18±3.77, p=0.000). AdjCmax (1.45±1.11 vs 1.81±1.30 ug*kg/ml/mg, p=0.014) and adjMPA-AUC0-720min (4.61±4.6 vs 5.98±4.67 hr*kg*ug/ml/mg, p=0.012) were also lower in the Eld group. Tmax occurred at 2.3±1.8h in both groups. Total body clearance (Clss_F) normalized by dose and weight and Terminal half life (HL_lambda_z) did not change between groups. These data indicate that elderly patients under TAC/MPS present a lower MPA oral bioavailability than younger ones but similar MPA clearance. These PK features may jeopardize the elderly recipients to reach MPA therapeutic window in the early phase but might limit overexposure to MPA along the first 6 months after transplantation.

To cite this abstract in AMA style:

Romano P, Agena F, Ebner P, Triboni A, Ramos F, Galante N, Lemos F, Sumita N, David-Neto E. Pharmacokinetics of Mycophenolic Acid (MPA) 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-mycophenolic-acid-mpa-in-elderly-compared-to-young-recipients-in-the-first-year-after-renal-transplantation-data-from-the-neverold-trial/. Accessed November 21, 2024.

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