P450 oxidoreductase *28 (POR*28) and tacrolimus disposition in pediatric kidney transplant recipients - A pilot study

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.