Evaluating the evidence for genotype-informed Bayesian dosing of tacrolimus in children undergoing solid organ transplantation: A systematic literature review.

Autor: Khatri D; Cancer Therapies, Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, Melbourne, VIC, Australia., Felmingham B; Cancer Therapies, Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, Melbourne, VIC, Australia., Moore C; Cancer Therapies, Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, Melbourne, VIC, Australia.; Department of Paediatrics, The University of Melbourne, Parkville, Melbourne, VIC, Australia., Lazaraki S; Health Sciences Library, Royal Melbourne Hospital, Melbourne Health, Australia., Stenta T; Cancer Therapies, Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, Melbourne, VIC, Australia., Collier L; Cancer Therapies, Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, Melbourne, VIC, Australia., Elliott DA; Cancer Therapies, Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, Melbourne, VIC, Australia.; Department of Paediatrics, The University of Melbourne, Parkville, Melbourne, VIC, Australia., Metz D; Department of Nephrology, The Royal Children's Hospital, Melbourne, VIC, Australia.; Murdoch Children's Research Institute, Melbourne, VIC, Australia.; Department of Paediatrics, Monash University, Melbourne, VIC, Australia., Conyers R; Cancer Therapies, Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, Melbourne, VIC, Australia.; Department of Paediatrics, The University of Melbourne, Parkville, Melbourne, VIC, Australia.; Children's Cancer Centre, The Royal Children's Hospital, Melbourne, VIC, Australia.
Jazyk: angličtina
Zdroj: British journal of clinical pharmacology [Br J Clin Pharmacol] 2024 Nov; Vol. 90 (11), pp. 2724-2741. Date of Electronic Publication: 2024 Aug 15.
DOI: 10.1111/bcp.16203
Abstrakt: Tacrolimus, a calcineurin inhibitor, is a highly effective immunosuppressant used in solid organ transplantation (SOT). However, it is characterized by a narrow therapeutic range and high inter-patient variability in pharmacokinetics. Standard weight-based dosing followed by empiric dose titration is suboptimal in controlling drug concentrations, increasing risk of rejection or toxicity, particularly in the initial months post transplantation. This review explores the potential of combined pre-transplant genotyping and pharmacokinetic (PK) modelling to improve tacrolimus dosing in paediatric SOT recipients. A systematic search of Medline, Embase and Cochrane databases identified studies published between March 2013 and March 2023 that investigated genotype- and PK model-informed tacrolimus dosing in children post-SOT. The Newcastle-Ottawa Scale assessed study quality. Seven studies encompassing paediatric kidney, heart, liver and lung transplants reported using genotype and model-informed dosing. A combination of clinical and genetic factors significantly impacts tacrolimus clearance and thus initial dose recommendation. Body size, transplant organ and co-medications were consistently important, while either time post-transplant or haematocrit emerged in some studies. Several models were identified, however, with limitations evident in some and with absence of evidence for their effectiveness in optimizing initial and subsequent dosing. This review highlights the development of PK models in paediatric SOT that integrate genotype and clinical covariates to personalize early tacrolimus dosing. While promising, prospective studies are needed to validate and confirm their effectiveness in improving time to therapeutic concentrations and reducing under- or overexposure. This approach has the potential to optimize tacrolimus therapy in paediatric SOT, thereby improving outcomes.
(© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Databáze: MEDLINE
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