title: Modeling of Tacrolimus Exposure in Kidney Transplant According to Posttransplant Time Based on Routine Trough Concentration Data.
abstract: OBJECTIVE
  The aim of this study was to develop a pharmacokinetics model allowing the description of the evolution of tacrolimus exposure in kidney transplant patients over the first months after transplant, using trough concentrations of routinely collected blood.
  
  
  METHODS
  The authors performed a retrospective analysis of trough concentration data collected from adult kidney transplant recipients (from 2008 to 2013). The total data set was divided into a building data set, used to build the structural model, and a validation data set, used to validate the structural model. (C0 = 133; 26 patients). A pharmacokinetics analysis was carried out by applying a nonparametric adaptive grid approach. The structural model parameters were tacrolimus clearance and volume of distribution.
  
  
  RESULTS
  In patients in the building set group, estimated clearance was 3.6 ± 0.57 L/h and estimated volume of distribution was 9.9 ± 1.14 L. No covariate was significantly associated with tacrolimus clearance or volume of distribution. The model adequately described tacrolimus dose-normalized trough concentration evolution after transplant (the plot of individual model predicted versus observed concentrations resulted in r = 0.84). The prediction performance in the validation group yielded 2.3% mean prediction error and 21.4% root mean squared error.
  
  
  CONCLUSIONS
  This model could be highly useful in the optimization of tacrolimus prescription at any posttransplant time in kidney transplant patients.
authors: From the Service de Pharmacologie, Faculté de Médecine, Monastir, Tunisia.
authors: Nadia
authors: N
authors: Ben Fredj
authors: Jean Baptiste
authors: JB
authors: Woillard
authors: Jean
authors: J
authors: Debord
authors: Amel
authors: A
authors: Chaabane
authors: Naceur
authors: N
authors: Boughattas
authors: Pierre
authors: P
authors: Marquet
authors: Franck
authors: F
authors: Saint-Marcoux
authors: Karim
authors: K
authors: Aouam
mesh_terms: D000293:Adolescent; D000328:Adult; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D015203:Reproducibility of Results; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014416:Tunisia; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016559:Tacrolimus