PMID- 36840340
OWN - NLM
STAT- MEDLINE
DCOM- 20230515
LR  - 20230517
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 16
IP  - 5
DP  - 2023 May
TI  - Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable 
      Black and White kidney transplant recipients: Implications for health inequities.
PG  - 861-871
LID - 10.1111/cts.13495 [doi]
AB  - Tacrolimus (TAC) and mycophenolic acid (MPA) provide maintenance 
      immunosuppression and is dosed empirically in elderly kidney transplant 
      recipients (KTRs) resulting in health inequities. Limited immunosuppressive 
      pharmacokinetics are available comparing adult ages. This secondary analysis 
      compared TAC and MPA pharmacokinetics and adverse effects (AEs) among young, 
      middle-aged, and elderly Black and White KTRs. The 12-h TAC and MPA 
      pharmacokinetics with AE evaluation were conducted in 67 stable KTRs greater than 
      or equal to 6 months post-transplant. TAC regimens were adjusted to target 
      troughs. MPA regimens were adjusted using clinical response. Participants were: 
      young: less than or equal to 40 years; middle age: greater than 40 to 60 years, 
      and elderly greater than 60 years. Noncompartmental pharmacokinetic analysis 
      determined area under the concentration-time curve 0-12 h (AUC(0-12h) ), 
      clearance (CL), and CL/body mass index (BMI) with 0-h troughs. MPA enterohepatic 
      recirculation (EHR), MPA-AUC(6-12h) /MPA-AUC(0-12h) , and MPA glucuronide 
      (MPAG)-AUC(0-12h) /MPA-AUC(0-12h) were determined. Univariate analysis of 
      variance (ANOVA) was conducted using SAS version 9.4. No group differences were 
      noted for estimated glomerular filtration rate, MPA, and TAC doses. EHR was 
      reduced in elderly with decreased MPA-AUC(6-12h) /MPA-AUC(0-12h) (p = 0.049) and 
      increased MPAG-AUC(0-12h) /MPA-AUC(0-12h) (p = 0.036). MPA troughs (p = 0.045) 
      were reduced in the elderly. TAC CL/BMI (p = 0.043) was reduced in the elderly. 
      For therapeutic MPA AUC(0-12h) : 30-60 mg.h/L, 34.3% KTRs achieved this target 
      with 55.2% greater than the therapeutic range. 77.6% KTR were in the TAC 
      AUC(0-12h) target: 100-190 ng.h/mL and 19.4% were below this range with no age 
      relationship. In 44% young, 26% middle-age and 7.8% elderly subjects achieved 
      target AUC(0-12h) for both medications (p = 0.036). Neurologic AEs were 
      manifested in the elderly (p = 0.014). Immunosuppressive pharmacokinetics 
      demonstrated age-related differences with reduced TAC CL/BMI and MPA EHR and 
      increased neurologic AE in the elderly. This immunosuppressive regimen may 
      require age-adjusted individualization to optimize allograft function.
CI  - (c) 2023 The Authors. Clinical and Translational Science published by Wiley 
      Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Tornatore, Kathleen M
AU  - Tornatore KM
AUID- ORCID: 0000-0003-2028-4998
AD  - Transplantation Immunosuppressive Pharmacology Research Program, Translational 
      Pharmacology Research Core, Department of Pharmacy Practice School of Pharmacy 
      and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA.
AD  - Department of Medicine, School of Medicine and Biomedical Sciences, University at 
      Buffalo, Buffalo, New York, USA.
FAU - Attwood, Kristopher
AU  - Attwood K
AD  - Department of Biostatistics, School of Public Health and Health Professions, 
      University at Buffalo, Buffalo, New York, USA.
FAU - Venuto, Rocco C
AU  - Venuto RC
AD  - Department of Medicine, School of Medicine and Biomedical Sciences, University at 
      Buffalo, Buffalo, New York, USA.
AD  - Division of Nephrology, Erie County Medical Center, University at Buffalo, 
      Buffalo, New York, USA.
FAU - Murray, Brian
AU  - Murray B
AD  - Department of Medicine, School of Medicine and Biomedical Sciences, University at 
      Buffalo, Buffalo, New York, USA.
AD  - Division of Nephrology, Erie County Medical Center, University at Buffalo, 
      Buffalo, New York, USA.
LA  - eng
GR  - R01 AG056392/AG/NIA NIH HHS/United States
GR  - R21 DK077325/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230413
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - WM0HAQ4WNM (Tacrolimus)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - 0 (Immunosuppressive Agents)
SB  - IM
MH  - Adult
MH  - Middle Aged
MH  - Aged
MH  - Humans
MH  - *Tacrolimus/adverse effects/pharmacokinetics
MH  - Mycophenolic Acid/adverse effects
MH  - *Kidney Transplantation/adverse effects
MH  - Area Under Curve
MH  - Immunosuppressive Agents/pharmacokinetics
MH  - Health Inequities
PMC - PMC10175981
COIS- The authors declared no competing interests for this work.
EDAT- 2023/02/26 06:00
MHDA- 2023/05/15 11:42
PMCR- 2023/04/13
CRDT- 2023/02/25 04:30
PHST- 2022/11/19 00:00 [received]
PHST- 2023/01/02 00:00 [accepted]
PHST- 2023/05/15 11:42 [medline]
PHST- 2023/02/26 06:00 [pubmed]
PHST- 2023/02/25 04:30 [entrez]
PHST- 2023/04/13 00:00 [pmc-release]
AID - CTS13495 [pii]
AID - 10.1111/cts.13495 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2023 May;16(5):861-871. doi: 10.1111/cts.13495. Epub 2023 Apr 
      13.