Therapeutic challenges of tacrolimus dose requirement and trough level in an indian pediatric renal transplant recipient with extensive metabolizer (Cytochrome P450 3A5*1)

Abstract

Pediatric patients need a higher dose of tacrolimus for posttransplant immunosuppression due to its high clearance. In addition, genetic polymorphism in cytochrome P450 (CYP) 3A5 enzyme (CYP3A5*1/*3) is an important determinant for its serum concentration. Substantial data exist about the requirement of higher doses of tacrolimus in patients with the CYP3A5*1 genotype (extensive metabolizer). Ketoconazole, an inhibitor of CYP, leads to the reduction of the tacrolimus dose while maintaining therapeutic levels in transplant recipients. However, very few studies have mentioned coadministration of ketoconazole and tacrolimus in pediatric renal transplant recipients. Herein, we present a case of a 10-year-old boy with end-stage renal disease due to posterior urethral valves who underwent a living-related kidney transplant. We also emphasize the importance of CYP3A5 genotype evaluation in deciding the course of the treatment and maintaining therapeutic levels of tacrolimus in pediatric transplant recipients.