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Population Pharmacokinetics of Tacrolimus in Umbilical Cord Blood Transplant Pediatrics


Tacrolimus was frequently used in umbilical cord blood transplant (UCBT) pediatrics for prevention of graft-vs-host disease (GVHD). The aim of the present study was to evaluate the population pharmacokinetics (PPK) of tacrolimus among UCBT pediatrics and find potential influenced factors. A total of 275 concentrations from 13 pediatrics were used to build a PPK model using a non-linear mixed-effects modelling approach. The impact of demographic features, biological characteristics, and concomitant medications, including sex, age, body weight, postoperative day, white blood cell (WBC), red blood cell (RBC), hemoglobin (HB), platelet (PLT), hematocrit (HCT), urea nitrogen (BUN), creatinine (Cr), aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBil), albumin (ALB), and total protein (TP) were investigated. The pharmacokinetics of tacrolimus were best described by a one-compartment model with first- and zero-order mixed absorption and first order elimination. The clearance (CL) and volume of distribution (V) of tacrolimus were 1.93 L/h and 75.1 L, respectively. A covariate analysis identified that postoperative day and co-administration with trimethroprim-sulfamethoxazole (TMP-SMZ) were significant covariates influencing CL of tacrolimus. Frequent blood monitoring and dose adjustment might need with the prolongation of postoperative day and co-administration with TMP-SMZ. This article is protected by copyright. All rights reserved.



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