title: Limited sampling strategies for tacrolimus exposure (AUC0-24) prediction after Prograf(®) and Advagraf(®) administration in children and adolescents with liver or kidney transplants.
abstract: To develop limited sampling strategies (LSSs) to predict total tacrolimus exposure (AUC0-24 ) after the administration of Advagraf(®) and Prograf(®) (Astellas Pharma S.A, Madrid, Spain) to pediatric patients with stable liver or kidney transplants. Forty-one pharmacokinetic profiles were obtained after Prograf(®) and Advagraf(®) administration. LSSs predicting AUC0-24 were developed by linear regression using three extraction time points. Selection of the most accurate LSS was made based on the r(2) , mean error, and mean absolute error. All selected LSSs had higher correlation with AUC0-24 than the correlation found between C0 and AUC0-24 . Best LSS for Prograf(®) in liver transplants was C0_1.5_4 (r(2)  = 0.939) and for kidney transplants C0_1_3 (r(2)  = 0.925). For Advagraf(®) , the best LSS in liver transplants was C0_1_2.5 (r(2)  = 0.938) and for kidney transplants was C0_0.5_4 (r(2)  = 0.931). Excluding transplant type variable, the best LSS for Prograf(®) is C0-1-3 (r(2)  = 0.920) and the best LSS for Advagraf(®) was C0_0.5_4 (r(2)  = 0.926). Considering transplant type irrespective of the formulation used, the best LSS for liver transplants was C0_2_3 (r(2)  = 0.913) and for kidney transplants was C0_0.5_4 (r(2)  = 0.898). Best LSS, considering all data together, was C0_1_4 (r(2)  = 0.898). We developed several LSSs to predict AUC0-24 for tacrolimus in children and adolescents with kidney or liver transplants after Prograf(®) and/or Advagraf(®) treatment.
authors.affiliation: Department of Pharmacology, School of Medicine, Autonomous University of Madrid, Madrid, Spain.
authors.forename: Gonzalo N
authors.initials: GN
authors.lastname: Almeida-Paulo
authors.forename: Rubin
authors.initials: R
authors.lastname: Lubomirov
authors.forename: Nazareth Laura
authors.initials: NL
authors.lastname: Alonso-Sanchez
authors.forename: Laura
authors.initials: L
authors.lastname: Espinosa-Román
authors.forename: Carlota
authors.initials: C
authors.lastname: Fernández Camblor
authors.forename: Carmen
authors.initials: C
authors.lastname: Díaz
authors.forename: Gema
authors.initials: G
authors.lastname: Muñoz Bartola
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Carcas-Sansuán
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D019540:Area Under Curve; D001800:Blood Specimen Collection / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation; D016014:Linear Models; D016031:Liver Transplantation; D008297:Male; D044469:Racial Groups; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: kidney; limited sampling strategies; liver; pediatric; tacrolimus; transplant