Longitudinal Pharmacokinetics of Mycophenolic Acid in Elderly Renal Transplant Recipients Compared to a Younger Control Group: Data from the nEverOld Trial.

BACKGROUND AND OBJECTIVES: Elderly patients are increasingly likely to be recipients of transplants. However, the pharmacokinetics of mycophenolic acid (MPA) in this population are yet to be studied in detail. The objective of this study was to assess whether there were differences in MPA pharmacokinetic parameter values between elderly recipients and younger-adult recipients during the 6 months immediately following renal transplantation. METHODS: In this analysis, the longitudinal 12-h pharmacokinetics of MPA, administered as enteric-coated mycophenolate sodium (EC-MPS), were evaluated in 44 elderly renal transplant recipients and compared with the corresponding pharmacokinetics of MPA in 31 younger adult recipients. Measurements were performed at 7, 30, 60, 90, and 180 days post-transplantation. All patients received tacrolimus and prednisone. RESULTS: The elderly patients were 30 years older than the younger controls, with a predominance of males and Caucasians. Elderly patients had lower serum albumin than the younger controls during the first 6 months after transplantation. The mean estimated total body MPA clearance of the elderly recipients was not significantly different from that of the controls at any analyzed time point (the mean clearance across all time points was 0.31 ± 0.17 vs 0.30 ± 0.25 L/h/kg). MPA exposure, as evaluated from the area under the 12-h time versus measured MPA concentration (adjusted for dose/body weight) curve, did not differ between the groups at any time point (mean exposure across all time points was 4.68 ± 3.61 vs 5.95 ± 4.29 µg·h/mL per mg/kg for the elderly recipients and the controls). CONCLUSIONS: These data show that the pharmacokinetics of MPA in elderly renal transplant recipients were no different to those of younger-adult recipients in this study population. CLINICALTRIALS.GOV: NCT 01631058.

Longitudinal Pharmacokinetics of Tacrolimus in Elderly Compared With Younger Recipients in the First 6 Months After Renal Transplantation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These data indicate that Eld recipients have a lower TAC clearance and therefore need a lower TAC dose than younger recipients.