A preliminary study searching for the right dose of tacrolimus in very young (≤4 years) renal transplant patients.
OBJECTIVE
The Radboudumc Amalia Children's hospital in the Netherlands has a programme for renal transplantation in children aged ≤4 years. Children receive chronic corticosteroid sparing immunosuppressive therapy that consists of tacrolimus and mycophenolate mofetil. This work aimed to describe the PK of tacrolimus in children ≤4 years with renal transplants.


METHODS
Paediatric renal transplant patients aged ≤4 years were included in this analysis. A PK curve of tacrolimus recorded ≤3 weeks after transplantation has been standard of care in our institution and aided in adjusting the dose in each patient to attain a target AUC0-12hof 210 μg h/l early after transplantation.


RESULTS
Eight patients were included. The first two patients received an initial twice-daily regimen and the subsequent six patients a three-times daily regimen. Median dose-corrected AUCtauwas 63 μg h/l. AUC target attainment was 37.5%. Of the remaining patients, two had an AUC very close to (around 10% below) the target.


CONCLUSIONS
Large interindividual variability of tacrolimus was observed and showed suboptimal AUC target attainment. In this population, an even more aggressive approach of higher doses (e.g. 0.4 mg/kg per day) and more early AUC determination should be considered. This should be evaluated prospectively in a larger group of patients.
Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands. lisa.martial@radboudumc.nl.|Radboud Institute for Health Sciences, Nijmegen, The Netherlands. lisa.martial@radboudumc.nl.
Lisa C
LC
Martial
Department of Paediatric Nephrology, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands.
Ruud H J
RH
Verstegen
Department of Paediatric Nephrology, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands.
Elisabeth A M
EA
Cornelissen
Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
Rob E
RE
Aarnoutse
Department of Paediatric Nephrology, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands.
Michiel F
MF
Schreuder
Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.|Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
Roger J M
RJ
Brüggemann
D000367:Age Factors; D019540:Area Under Curve; D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D002675:Child, Preschool; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D007223:Infant; D016030:Kidney Transplantation / Q000009:adverse effects; D009426:Netherlands; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016559:Tacrolimus
children; immunosuppressant; pharmacokinetics; therapeutic drug monitoring; transplantation