Elsevier

Clinical Therapeutics

Volume 24, Issue 3, March 2002, Pages 330-350
Clinical Therapeutics

Therapeutic drug monitoring of immunosuppressant drugs in clinical practice

https://doi.org/10.1016/S0149-2918(02)85038-XGet rights and content

Abstract

Background: Therapeutic drug monitoring (TDM) is essential to maintain the efficacy of many immunosuppressant drugs while minimizing their toxicity. TDM has become more refined with the development of new monitoring techniques and more specific assays.

Objective: This article summarizes current data on TDM of the following immunosuppressant drugs used in organ transplantation: cyclosporine, tacrolimus, sirolimus, everolimus, and mycophenolate mofetil.

Methods: Published data were identified by a MEDLINE search of the English-language literature through March 2001 using the terms therapeutic drug monitoring, cyclosporine, tacrolimus, sirolimus, everolimus, and mycophenolate mofetil. Relevant conference abstracts were also included.

Results: TDM of cyclosporine has been well studied, and recent findings indicate that monitoring of drug levels 2 hours after dosing is a more sensitive predictor of outcome than trough (C0) monitoring. C0 levels are being used more widely in TDM of tacrolimus; however, the relationship between C0 and area under the curve has varied widely in clinical trials, with correlations ranging from 0.11 to 0.92. The use of TDM of sirolimus, everolimus, and mycophenolate mofetil is evolving rapidly.

Conclusions: TDM of immunosuppressant drugs that have a narrow therapeutic index is an increasingly useful tool for minimizing drug toxicity while maximizing prevention of graft loss and organ rejection.

References (85)

  • H Podder et al.

    Impact of sirolimus on renal transplant outcomes in African Americans

    Transplant Proc

    (2001)
  • A MacDonald et al.

    Clinical pharmacokinetics and therapeutic drug monitoring of sirolimus

    Clin Ther

    (2000)
  • BD Kahan et al.

    Role of therapeutic drug monitoring of rapamycin

    Transplant Proc

    (1998)
  • K Peltekian et al.

    De novo use of low-dose tacrolimus and sirolimus in liver transplantation

    Transplant Proc

    (2001)
  • LM Shaw et al.

    Pharmacokinetic, pharmacodynamic, and outcome investigations as the basis for mycophenolic acid therapeutic drug monitoring in renal and heart transplant recipients

    Clin Biochem

    (2001)
  • BM Meiser et al.

    Combination therapy with tacrolimus and mycophenolate mofetil following cardiac transplantation: Importance of mycophenolic acid therapeutic drug monitoring

    J Heart Lung Transplant

    (1999)
  • D DeNofrio et al.

    Mycophenolic acid concentrations are associated with cardiac allograft rejection

    J Heart Lung Transplant

    (2000)
  • M Salvadori

    Therapeutic equivalence of mycophenolate sodium versus mycophenolate mofetil in de novo renal transplant recipients

    Transplant Proc

    (2001)
  • S Hariharan et al.

    Improved graft survival after renal transplantation in the United States, 1988 to 1996

    N Engl J Med

    (2000)
  • A Johnston et al.

    Therapeutic drug monitoring of immunosuppressant drugs

    Br J Clin Pharmacol

    (1999)
  • A Lindholm et al.

    Pharmacokinetics and therapeutic drug monitoring of immunosuppressants

    Ther Drug Monit

    (1995)
  • A Lindholm et al.

    Influence of cyclosporine pharmacokinetics, trough concentrations, and AUC monitoring on outcome after kidney transplantation

    Clin Pharmacol Ther

    (1993)
  • K Mahalati et al.

    Absorption profiling: A novel method for monitoring Neoral in kidney transplantation that reduces rejection and nephrotoxicity

    Transplantation

    (2000)
  • P Belitsky et al.

    Impact of absorption profiling on efficacy and safety of cyclosporin therapy in transplant recipients

    Clin Pharmacokinet

    (2000)
  • BD Kahan et al.

    Variable oral absorption of cyclosporine. A biopharmaceutical risk factor for chronic renal allograft rejection

    Transplantation

    (1996)
  • BD Kahan et al.

    Low intraindividual variability of cyclosporin A exposure reduces chronic rejection incidence and health care costs

    J Am Soc Nephrol

    (2000)
  • K Mahalati et al.

    Neoral monitoring by simplified sparse sampling area under the concentration-time curve: Its relationship to acute rejection and cyclosporine nephrotoxicity early after kidney transplantation

    Transplantation

    (1999)
  • RP Kershner et al.

    Relationship of FK506 whole blood concentrations and efficacy and toxicity after liver and kidney transplantation

    Transplantation

    (1996)
  • N Undre et al.

    Pharmacokinetic interpretation of FK 506 levels in blood and in plasma during a European randomised study in primary liver transplant patients

    Transplant Int

    (1994)
  • BD Kahan et al.

    Therapeutic drug monitoring of sirolimus: Correlations with efficacy and toxicity

    Clin Transplant

    (2000)
  • BD Kahan

    Cyclosporine

    N Engl J Med

    (1989)
  • BD Kahan et al.

    Consensus document: Hawk's Cay meeting on Therapeutic Drug Monitoring of Cyclosporine

    Clin Chem

    (1990)
  • LM Shaw et al.

    Critical issues in cyclosporine monitoring: Report of the Task Force on Cyclosporine Monitoring

    Clin Chem

    (1987)
  • J Grevel et al.

    Area under the curve monitoring of cyclosporine therapy: The early posttransplant period

    Ther Drug Monit

    (1991)
  • TJ Schroeder et al.

    Relationship between cyclosporine bioavailability and clinical outcome in renal transplant recipients

    Transplant Proc

    (1994)
  • MF Senel et al.

    Impact of early cyclosporin average blood concentration on early kidney transplant failure

    Transplant Int

    (1998)
  • A Johnston et al.

    A limited sampling strategy for the measurement of cyclosporine AUC

    Transplant Proc

    (1990)
  • A Johnston et al.

    Predicting patients' exposure to cyclosporin

    Transplant Int

    (1996)
  • AJ Amante et al.

    Abbreviated AUC strategy for monitoring cyclosporine microemulsion therapy in the immediate posttransplant period

    Transplant Proc

    (1996)
  • J Grevel et al.

    Abbreviated kinetic profiles in area-under-the-curve monitoring of cyclosporine therapy

    Clin Chem

    (1991)
  • P Keown

    Experience with use of sparse-sample—derived AUCs for management of Neoral®

  • P Keown et al.

    A randomized, prospective multicenter pharmacoepidemiologic study of cyclosporine microemulsion in stable renal graft recipients. Report of the Canadian Neoral Renal Transplantation Study Group

    Transplantation

    (1996)

    • Cited by (0)

    View full text
    Copyright © 2002 Published by Elsevier Inc.