Clinical aspects of tacrolimus use in paediatric renal transplant recipients

Pediatric Nephrology : Journal of the International Pediatric Nephrology Association
Agnieszka Prytuła, Teun van Gelder

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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Citations

May 14, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Tian Xia, Yanfeng Wang
Sep 15, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Karmila Abu BakarJon Jin Kim
Jul 31, 2018·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Agnieszka PrytułaAnn Raes
Sep 24, 2020·Transplant International : Official Journal of the European Society for Organ Transplantation·Agnieszka Prytuła

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