Lisa C Martial1,2, Ruud H J Verstegen3, Elisabeth A M Cornelissen3, Rob E Aarnoutse4,5, Michiel F Schreuder3, Roger J M Brüggemann4,5. 1. Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands. lisa.martial@radboudumc.nl. 2. Radboud Institute for Health Sciences, Nijmegen, The Netherlands. lisa.martial@radboudumc.nl. 3. Department of Paediatric Nephrology, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands. 4. Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands. 5. Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
Abstract
OBJECTIVES: 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 AUC0-12h of 210 μg h/l early after transplantation. KEY FINDINGS: 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 AUCtau was 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.
OBJECTIVES: 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 AUC0-12h of 210 μg h/l early after transplantation. KEY FINDINGS: 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 AUCtau was 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.
Authors: Anne M Schijvens; Fransje H S van Hesteren; Elisabeth A M Cornelissen; Charlotte M H H T Bootsma-Robroeks; Roger J M Brüggemann; David M Burger; Saskia N de Wildt; Michiel F Schreuder; Rob Ter Heine Journal: Pediatr Nephrol Date: 2018-10-30 Impact factor: 3.714