title: Choosing the right dose of tacrolimus.
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).
authors.affiliation: Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France EA7323, Université Paris Diderot-Université Paris Descartes, Paris, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Lancia
authors.affiliation: 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.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Jacqz-Aigrain
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D002648:Child; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D016377:Organ Transplantation / Q000379:methods; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D007166:Immunosuppressive Agents; D051544:Cytochrome P-450 CYP3A; D009173:Mycophenolic Acid; D016559:Tacrolimus