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Clinical aspects of tacrolimus use in paediatric renal transplant recipients

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Abstract

The calcineurin inhibitor tacrolimus, cornerstone of most immunosuppressive regimens, is a drug with a narrow therapeutic window: underexposure can lead to allograft rejection and overexposure can result in an increased incidence of infections, toxicity and malignancies. Tacrolimus is metabolised in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. This review focusses on the clinical aspects of tacrolimus pharmacodynamics, such as efficacy and toxicity. Factors affecting tacrolimus pharmacokinetics, including pharmacogenetics and the rationale for routine CYP3A5*1/*3 genotyping in prospective paediatric renal transplant recipients, are also reviewed. Therapeutic drug monitoring, including pre-dose concentrations and pharmacokinetic profiles with the available “reference values”, are discussed. Factors contributing to high intra-patient variability in tacrolimus exposure and its impact on clinical outcome are also reviewed. Lastly, suggestions for future research and clinical perspectives are discussed.

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Authors and Affiliations

  1. Paediatric Nephrology and Rheumatology Department, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium

    Agnieszka Prytuła

  2. Hospital Pharmacy and Internal Medicine Departments, Erasmus Medical Center, Rotterdam, The Netherlands

    Teun van Gelder

Authors
  1. Agnieszka Prytuła
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  2. Teun van Gelder
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Correspondence to Agnieszka Prytuła.

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Answers: 1. a; 2. d; 3. d; 4. b; 5. c

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Prytuła, A., van Gelder, T. Clinical aspects of tacrolimus use in paediatric renal transplant recipients. Pediatr Nephrol 34, 31–43 (2019). https://doi.org/10.1007/s00467-018-3892-8

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  • DOI: https://doi.org/10.1007/s00467-018-3892-8

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