Population Pharmacokinetics of Tacrolimus in Pediatric Patients With Umbilical Cord Blood Transplant

Abstract

Tacrolimus was frequently used in pediatric patients with umbilical cord blood transplant for the prevention of graft-versus-host disease. The aim of the present study was to evaluate the population pharmacokinetics of tacrolimus among pediatric patients with umbilical cord blood transplant and find potential influenced factors. A total of 275 concentrations from 13 pediatric patients were used to build a polulation pharmacokinetic model using a nonlinear mixed-effects modeling approach. The impact of demographic features, biological characteristics, and concomitant medications, including sex, age, body weight, postoperative day, white blood cell count, red blood cell count, hemoglobin, platelets, hematocrit, blood urea nitrogen, creatinine, aspartate transaminase, alanine transaminase, total bilirubin, albumin, and total protein were investigated. The pharmacokinetics of tacrolimus were best described by a 1-compartment model with first-and zero-order mixed absorption and first-order elimination. The clearance and volume of distribution of tacrolimus were 1.93 L/h and 75.1 L, respectively. A covariate analysis identified that postoperative day and co-administration with trimethoprim-sulfamethoxazole were significant covariates influencing clearance of tacrolimus. Frequent blood monitoring and dose adjustment might be needed with the prolongation of postoperative day and coadministration with trimethoprim-sulfamethoxazole.