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      Choosing the right dose of tacrolimus.

      1 , 2 , 3
      Archives of disease in childhood
      BMJ

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          Abstract

          Choosing the right dose of tacrolimus 'adapted to each individual patient' is a central question after transplantation. The pharmacokinetic behaviour of tacrolimus in paediatric patients is significantly influenced by clinical factors growth and maturation, as well as genetic factors. Large interindividual variability and narrow therapeutic index make dosage individualisation mandatory in children. CYP3A5 expressers require a 1.8-fold higher tacrolimus dose than non-expressers. A visual patient-tailored dosing chart, taking into consideration the child's weight, recent haematocrit level and CYP3A5 genotype, was developed based on a population pharmacokinetic-pharmacogenetic model, and can be used routinely to individualise tacrolimus starting dose. Area under the concentration-time curve-based dosage adaptation through limited sampling strategy and Bayesian estimation is more reliable than trough concentration. Therapeutic drug monitoring and dosage adaptation can be included in routine post-transplantation consultation and should be considered in the urgent situations (eg, rejection, adverse event, lack of compliance, change of coadministration drug with potential drug-drug interaction and other situations).

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          Author and article information

          Journal
          Arch. Dis. Child.
          Archives of disease in childhood
          BMJ
          1468-2044
          0003-9888
          Apr 2015
          : 100
          : 4
          Affiliations
          [1 ] Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France EA7323, Université Paris Diderot-Université Paris Descartes, Paris, France.
          [2 ] Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France EA7323, Université Paris Diderot-Université Paris Descartes, Paris, France Clinical Investigation Center CIC1426, INSERM, Paris, France.
          [3 ] Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France EA7323, Université Paris Diderot-Université Paris Descartes, Paris, France Clinical Investigation Center CIC1426, INSERM, Paris, France Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan, China.
          Article
          archdischild-2013-305888
          10.1136/archdischild-2013-305888
          25416736
          c20454b4-ea84-4589-9354-79f152eada10
          History

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