Limited sampling strategies for tacrolimus exposure (AUC0‐24) prediction after Prograf® and Advagraf® administration in children and adolescents with liver or kidney transplants

Summary 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 r2, 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 (r2 = 0.939) and for kidney transplants C0_1_3 (r2 = 0.925). For Advagraf®, the best LSS in liver transplants was C0_1_2.5 (r2 = 0.938) and for kidney transplants was C0_0.5_4 (r2 = 0.931). Excluding transplant type variable, the best LSS for Prograf® is C0-1-3 (r2 = 0.920) and the best LSS for Advagraf® was C0_0.5_4 (r2 = 0.926). Considering transplant type irrespective of the formulation used, the best LSS for liver transplants was C0_2_3 (r2 = 0.913) and for kidney transplants was C0_0.5_4 (r2 = 0.898). Best LSS, considering all data together, was C0_1_4 (r2 = 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.