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Abstract: PO2365

Tacrolimus and Mycophenolic Acid Pharmacokinetics in Young, Middle-Aged, and Elderly Stable Renal Transplant Recipients

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Tornatore, Kathleen M., University at Buffalo - The State University of New York, Buffalo, New York, United States
  • Attwood, Kris, Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States

Group or Team Name

  • Transplantation Immunosuppressive Pharmacology Research Program
Background

Tacrolimus (TAC) and mycophenolic acid (MPA) comprise a critical maintenance immunosuppressive regimen. Limited pharmacokinetic data are available comparing age-related differences of these immunosuppressive drugs which is an important fact considering the increase in renal transplants in older patients. This analysis compared TAC and MPA pharmacokinetics among young, middle age and elderly stable renal transplant recipients (RTR).

Methods

Twelve-hour TAC and MPA pharmacokinetic studies were conducted in 67 stable RTR at least 1-year post renal transplant. Tacrolimus dose regimens were adjusted to troughs (4 to 10 ng/ml) based upon time post-transplant. MPA regimens were adjusted using clinical responses only. Patients were categorized as: young: >21 & ≤ 40 years; middle age: >40 &≤ 60 years and elderly>60 years. Non-compartmental pharmacokinetic analysis determined area under the concentration-time curve 0-12hours (AUC0-12), AUC4-12/AUC0-12 (to define MPA enterohepatic recirculation), apparent clearance (CL) normalized to BMI (CL/BMI) and 0 hour troughs. Univariate ANOVA was conducted using SAS V 9.4.

Results

Table 1 summarizes the results. No group differences were noted for estimated glomerular filtration rate, MPA and TAC doses. Enterohepatic recirculation and MPA troughs were reduced in elderly compared to young. For MPA target AUC0-12hr of 30 to 60 mg.hr/L, 34.3% of RTR achieved this range with 56.7% above this therapeutic exposure. There were 52.2% of RTR within the therapeutic tacrolimus AUC0-12hr target of 120-200 ng.hr/ml with 46.1% below this range with no age relationship. Reduced tacrolimus CL/BMI was noted in elderly compared to middle age.

Conclusion

Tacrolimus and mycophenolic acid pharmacokinetics demonstrates age-related differences with lower clearances or exposures in the elderly. Tacrolimus and mycophenolic acid immunosuppression may require age-adjusted individualization to achieve therapeutic exposure.

Tacrolimus and Mycophenolic Acid Pharmacokinetics by Age
Endpoints ( Mean[SD])Young(N=16)Middle Age(N=38)Elderly(N=13)P Value
MPA trough(mg/L)5.8(3.6)4.8(5.2)3.3(3.6)0.045*
MPA AUC4-12/AUC0-120.55(0.14)0.51(0.15)0.42(0.13)0.047*
MPA CL/BMI0.35(0.17)0.38(0.19)0.31(0.10)0.539
TAC trough (ng/ml)6.8(1.6)6.9(1.9)6.7(1.7)0.948
TAC CL/BMI1.01 (0.51)1.01(0.51)0.68(0.38)0.055+

*: Significant +: Trend toward significant

Funding

  • NIDDK Support