Pharmacokinetics and Toxicity of Tacrolimus Early After Heart and Lung Transplantation

M.A. Sikma*, E.M. van Maarseveen, E.A. van de Graaf, J.H. Kirkels, M.C. Verhaar, D.W. Donker, J. Kesecioglu, J. Meulenbelt

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

75 Citations (Scopus)
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Abstract

Annually, about 8000 heart and lung transplantations are successfully performed worldwide. However, morbidity and mortality still pose a major concern. Renal failure in heart and lung transplant recipients is an essential adverse cause of morbidity and mortality, often originating in the early postoperative phase. At this time of clinical instability, the kidneys are exposed to numerous nephrotoxic stimuli. Among these, tacrolimus toxicity plays an important role, and its pharmacokinetics may be significantly altered in this critical phase by fluctuating drug absorption, changed protein metabolism, anemia and (multi-) organ failure. Limited understanding of tacrolimus pharmacokinetics in these circumstances is hampering daily practice. Tacrolimus dose adjustments are generally based on whole blood trough levels, which widely vary early after transplantation. Moreover, whole blood trough levels are difficult to predict and are poorly related to the area under the concentration-time curve. Even within the therapeutic range, toxicity may occur. These shortcomings of tacrolimus monitoring may not hold for the unbound tacrolimus plasma concentrations, which may better reflect tacrolimus toxicity. This review focuses on posttransplant tacrolimus pharmacokinetics, discusses relevant factors influencing the unbound tacrolimus concentrations and tacrolimus (nephro-) toxicity in heart and lung transplantation patients.
Original languageEnglish
Pages (from-to)2301-2313
Number of pages13
JournalAmerican journal of transplantation
Volume15
Issue number9
DOIs
Publication statusPublished - Sep 2015
Externally publishedYes

Keywords

  • calcineurin inhibitor: tacrolimus
  • critical care
  • intensive care management
  • drug toxicity
  • immunosuppressant
  • patient safety
  • pharmacokinetics
  • pharmacodynamics
  • CHRONIC KIDNEY-DISEASE
  • HEALTHY-HUMAN SUBJECTS
  • CYSTIC-FIBROSIS
  • P-GLYCOPROTEIN
  • INTERNATIONAL SOCIETY
  • MYCOPHENOLATE-MOFETIL
  • LIVER-TRANSPLANTATION
  • RENAL-TRANSPLANTATION
  • GENETIC POLYMORPHISMS
  • SEQUENCE DIVERSITY

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