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Choosing the right dose of tacrolimus
  1. Pauline Lancia1,2,
  2. Evelyne Jacqz-Aigrain1,2,3,
  3. Wei Zhao1,2,3,4
  1. 1Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France
  2. 2EA7323, Université Paris Diderot-Université Paris Descartes, Paris, France
  3. 3Clinical Investigation Center CIC1426, INSERM, Paris, France
  4. 4Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan, China
  1. Correspondence to Professor Dr Wei Zhao, Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; wei.zhao{at}


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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