title: Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation.
abstract: OBJECTIVE
  The purpose of this study was to describe the population pharmacokinetics (PK) of tacrolimus (TAC) in 52 Chinese pediatric patients early after liver transplantation.
  
  
  METHODS
  Details of drug dose, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data from the first day after surgery. A total of 488 concentration data were obtained and analyzed by a nonlinear mixed-effect modeling (NONMEM) method. A number of demographic and clinical variables were tested for their influence on TAC PK parameters.
  
  
  RESULTS
  The PK of TAC were best described by a one-compartment model with first-order absorption and elimination. Apparent clearance (CL/F) and apparent volumes of distribution (V/F) in final population model were 5.72 L/h and 131 L, respectively. The absorption rate constant (Ka) was fixed in 4.48 h-1. The inter-individual variabilities in CL/F and V/F were 13.5% and 78.1%. In the final analysis performed in all 52 patients, the post-operation day (POD) and alanine aminotransferase (ALT) influenced TAC CL/F and V/F, and total protein (TP) was the only covariate retained on V/F.
  
  
  CONCLUSIONS
  A population PK model of TAC was developed in Chinese pediatric patients early after liver transplantation. It identified significant relationships between the PK of TAC and the characteristics of the patients. POD, ALT, and TP were identified as the main factors influencing the PK of TAC. The developed model could be useful to optimize individual pediatric TAC dosing regimen in routine clinical practice.
authors.forename: Jian-wei
authors.initials: JW
authors.lastname: Yang
authors.forename: Sha-sha
authors.initials: SS
authors.lastname: Liao
authors.forename: Li-qin
authors.initials: LQ
authors.lastname: Zhu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao-ye
authors.initials: XY
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Rao
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.forename: Wen-zhuo
authors.initials: WZ
authors.lastname: Li
authors.forename: Li-ying
authors.initials: LY
authors.lastname: Sun
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D019540:Area Under Curve; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D002681:China; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000208:ethnology / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007223:Infant; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D017711:Nonlinear Dynamics; D015203:Reproducibility of Results; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus