ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Advanced Search

Target Tacrolimus Troughs and CYP3A5 Polymorphisms Do Not Predict Therapeutic Drug Exposure in African American and Caucasian Renal Transplant Recipients

K. Tornatore,1,4 K. Attwood,2 D. Brazeau,3 S. Chang,4 R. Venuto.4

1Pharmacy, School of Pharmacy, University at Buffalo(UB), Buffalo
2Biostatistics, RPCI, Buffalo
3Pharmaceutical Sciences, University of New England, Portland
4Nephrology, UB School of Medicine, Buffalo.

Meeting: 2018 American Transplant Congress

Abstract number: C105

Keywords: African-American, FK506, Immunosuppression, Kidney transplantation

Session Information

Date: Monday, June 4, 2018

Session Name: Poster Session C: Kidney Immunosuppression: Novel Regimens and Drug Minimization

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall 4EF

Related Abstracts
  • Association of CYP3A5*3*6*7 Metabolic Composites to Tacrolimus Pharmacokinetics in African American and Caucasian Renal Transplant Recipients
  • Differences in Tacrolimus Troughs and Doses Between Caucasians and African Americans with Two CYP3A5 Loss-of-Function Alleles: Looking Beyond CYP3A5 Expression.

Background: African American(AA) renal transplant recipients(RTR) require larger tacrolimus(TAC) doses to achieve similar troughs to Caucasians which may be due to CYP3A5 polymorphisms. TAC pharmacokinetics exhibits interpatient variability requiring trough monitoring and racial investigation of corresponding area under concentration-time curves(AUC0-12hr) is limited. The relationship between TAC trough(target:4-9ng/ml),AUC0-12hr and CYP3A5 variants was investigated in 65 stable AA and Caucasian RTR >6 months post-transplant treated with TAC and mycophenolic acid.

Methods: 12-hour serial samples determined steady-state TAC AUC0-12 and 12hr troughs(C-12hr). The CYP3A5 polymorphisms: *3[rs776746],*6[10264272],*7[41303343], associated with loss of protein function, were characterized. RTR were classified as Extensive, Intermediate and Poor metabolizers using the novel CYP3A5*3*6*7 metabolic composites based on functional genes present and analyzed by SAS V 9.4.

Results: Table 1 summarizes the results. Although 98.5% RTR achieved therapeutic troughs of 4-12ng/ml, 30 of 65(46.2%) patients had AUC0-12 < target 120-200 mg▪h/ml. More AA were in the desired AUC0-12 range than Caucasians. No association of CYP3A5 variants with RTR in or below AUC0-12 range was found.

[dagger]=Mean±SD AA [N=33] C [N=32] P-Value
TAC Dose(mg)[dagger] 4.2±1.8 2.4±1.1 <0.001
TAC C-12hr(ng/ml)[dagger] 7.8±1.8 6.7±1.8 0.010
C-12hr at target:4-12 ng/ml 33(100%) 31(96%) 0.49
C-12hr below target 1(3.1%)
TAC AUC0-12hr [dagger] 137.0±78.9 114.6±28.0 0.005
AUC0-12hr at target:120-200 mg▪hr/ml 23(69.7%) 12(37.5%) 0.013
AUC0-12hr below target 10(30.3%) 20(62.5%)
Poor CYP3A5 6(18.2%) 29(90.6%) <0.001
Intermediate CYP3A5 20(60.6%) 3(9.4%)
Extensive CYP3A5 7(21.1%)

Conclusion: Most RTR attained therapeutic troughs but did not consistently achieve target tacrolimus AUC0-12hr with no association to CYP3A5 variants noted. Additional pharmacokinetic factors must be investigated.

CITATION INFORMATION: Tornatore K., Attwood K., Brazeau D., Chang S., Venuto R. Target Tacrolimus Troughs and CYP3A5 Polymorphisms Do Not Predict Therapeutic Drug Exposure in African American and Caucasian Renal Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Tornatore K, Attwood K, Brazeau D, Chang S, Venuto R. Target Tacrolimus Troughs and CYP3A5 Polymorphisms Do Not Predict Therapeutic Drug Exposure in African American and Caucasian Renal Transplant Recipients [abstract]. https://atcmeetingabstracts.com/abstract/target-tacrolimus-troughs-and-cyp3a5-polymorphisms-do-not-predict-therapeutic-drug-exposure-in-african-american-and-caucasian-renal-transplant-recipients/. Accessed March 8, 2021.

« Back to 2018 American Transplant Congress

Most Viewed Abstracts

  • This Week
  • This Month
  • All Time
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Live Related Kidney Transplant Experience in Abuja, Nigeria – First Eight Cases Ever.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • A Decade of Donor-Derived Disease: A Report of the OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC).
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Evidence of a Clinically Significant Drug-Drug Interaction between Cannabidiol and Tacrolimus: A Case Report
  • Kidney Dialysis after Heart Transplantation: The Short and Long Term Outcomes

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2021 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy

loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.