Violette M G J Gijsen1, Ron H N van Schaik, Offie P Soldin, Steven J Soldin, Irena Nulman, Gideon Koren, Saskia N de Wildt. 1. *Intensive Care and Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands; †Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, ON, Canada; ‡Department of Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands; Departments of §Oncology; ¶Medicine; ‖Pharmacology; **Physiology; ††Biophysics, Georgetown University Medical Center, Washington, DC; and ‡‡Department of Medicine, University of Western Ontario, London, ON, Canada.
Abstract
BACKGROUND: Both age and CYP3A5 genotype are important determinants of tacrolimus disposition in pediatric kidney transplant recipients. In a recent study in adults, POR*28 was associated with increased dosing requirements early after transplant of CYP3A5-expressing kidney transplant recipients. The authors aimed to evaluate the additional contribution of POR*28 to early tacrolimus disposition in pediatric kidney transplant recipients. METHODS: Retrospective data of 43 pediatric kidney transplant recipients up to 14 days posttransplant were evaluated on tacrolimus dose and tacrolimus predose blood concentrations. Recipient POR*28 and CYP3A5 genotype were determined. RESULTS: CYP3A5 expressers carrying at least 1 POR*28 allele had on average 18.3% lower tacrolimus predose concentrations and 20.2% lower concentration/dose ratios compared with CYP3A5 expressers with POR*1/*1 genotype (P = 0.002 and P = 0.001, respectively). In CYP3A5 nonexpressers, tacrolimus disposition did not significantly differ between POR genotypes. CONCLUSIONS: In this small cohort of pediatric kidney transplant recipients, POR*28 genotype seems to explain part of the variability found in tacrolimus disposition, in addition to age and CYP3A5 genotype. This finding should be validated in a larger population, and it would be worthwhile to evaluate the clinical impact of this genotype.
BACKGROUND: Both age and CYP3A5 genotype are important determinants of tacrolimus disposition in pediatric kidney transplant recipients. In a recent study in adults, POR*28 was associated with increased dosing requirements early after transplant of CYP3A5-expressing kidney transplant recipients. The authors aimed to evaluate the additional contribution of POR*28 to early tacrolimus disposition in pediatric kidney transplant recipients. METHODS: Retrospective data of 43 pediatric kidney transplant recipients up to 14 days posttransplant were evaluated on tacrolimus dose and tacrolimus predose blood concentrations. Recipient POR*28 and CYP3A5 genotype were determined. RESULTS:CYP3A5 expressers carrying at least 1 POR*28 allele had on average 18.3% lower tacrolimus predose concentrations and 20.2% lower concentration/dose ratios compared with CYP3A5 expressers with POR*1/*1 genotype (P = 0.002 and P = 0.001, respectively). In CYP3A5 nonexpressers, tacrolimus disposition did not significantly differ between POR genotypes. CONCLUSIONS: In this small cohort of pediatric kidney transplant recipients, POR*28 genotype seems to explain part of the variability found in tacrolimus disposition, in addition to age and CYP3A5 genotype. This finding should be validated in a larger population, and it would be worthwhile to evaluate the clinical impact of this genotype.
Authors: G N Almeida-Paulo; I Dapía García; R Lubomirov; A M Borobia; N L Alonso-Sánchez; L Espinosa; A J Carcas-Sansuán Journal: Pharmacogenomics J Date: 2017-01-17 Impact factor: 3.550
Authors: Noël Knops; Jean Herman; Maria van Dyck; Yasaman Ramazani; Edward Debbaut; Rita van Damme-Lombaerts; Elena Levtchenko; Lambertus P van den Heuvel; Steffen Fieuws; Dirk Kuypers Journal: Br J Clin Pharmacol Date: 2016-12-13 Impact factor: 4.335