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.

Keywords: kidney; limited sampling strategies; liver; pediatric; tacrolimus; transplant.