Abstract: SA-PO641

Age Influences on Tacrolimus Pharmacokinetics Post-Transplant

Session Information

Category: Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics

  • 1601 Pharmacokinetics, Pharmacodynamics, Pharmacogenomics

Authors

  • Tornatore, Kathleen M., School of Pharmacy and Pharmaceutical Sciences; Erie County Medical Center, Buffalo, New York, United States
  • Attwood, Kris, School of Public Health, Buffalo, New York, United States
  • Venuto, Rocco C., Erie County Medical Center, Buffalo, New York, United States
Background

Minimal data is available describing the influence of age on tacrolimus (TAC) pharmacokinetics (PK) in African American (AA) and Caucasian (C) renal transplant recipients (RTR) in spite of increased renal transplantation in the elderly. This sub-study investigated the impact of age on TAC PK in stable AA and C RTR.

Methods

The 12-hour PK study of TAC was investigated in 35 AA and 32 C RTR receiving enteric coated MPA and tacrolimus. Cumulative adverse effects (CAE) were assessed including gastrointestinal, neurologic and aesthetic manifestations. Patents were categorized by age as follows: Young: >21 & ≤ 40 years; Middle Age: >40 &≤ 60 years and Elderly>60 years. Apparent clearance (CL), BMI normalized CL (CL/BMI), Area Under the Concentration-time curve 0-12h (AUC12), dose-normalized AUC12 (AUC*), 12 hour troughs (C-12h) and dose normalized C-12hr(C-12h/Dose) with CAE were determined and analyzed with univariate ANOVA.

Results

Table summarizes the results. All group means were within the therapeutic AUC12 guide of 120-200 mg.hr/ml for TAC. The elderly received the lowest TAC dose and achieved comparable, therapeutic C-12h troughs and AUC12 to other groups. The elderly had a higher dose normalized trough and AUC* with slower CL and more CAE compared to younger patients.

Conclusion

These findings suggest that TAC dosing regimens need be individualized based upon adult ages and time post transplant. Further investigations into age-related changes in TAC exposure and relation to clinical responses(i.e. adverse effects) remain important for safe and efficacious immunosuppression.

EndpointsYoung(n=16)Middle Age(n=38)Elderly(n=13)P Value
e-GFR57.06 (16.04)52.97(14.26)59.40 (19.26)0.390
TAC Dose(mg)3.3(1.4)3.6(1.9)2.7 (1.6)0.257
MPA Dose (mg)641.3 (185.5)630.0(176.3)595.4(135.2)0.757
C-12h (ng/ml)7.0(1.5)7.1(2.0)7.6(1.9)0.715
C-12h/Dose2.4(1.0)2.6(1.6)3.4(1.5)0.011*
AUC12 (ng.hr/ml)126.0(31.1)124.6(33.8)126.7(31.4)0.976
AUC*41.2(14.2)44.3(25.0)56.2(23.3)0.037*
CL (L/hr)28.1(11.9)29.1(14.6)21.8(11.1)0.034*
CL/BMI1.01 (0.51)1.01(0.51)0.68(0.38)0.043+
CAE Score0.13 (0.09)0.14 (0.08)0.15 (0.05)0.064*
     

* Time Post-Transplant Adjusted Analysis

Funding

  • NIDDK Support