TY - JOUR
T1 - A limited sampling strategy to estimate exposure of once-daily modified release tacrolimus in renal transplant recipients using linear regression analysis and comparison with Bayesian population pharmacokinetics in different cohorts
AU - Stifft, Frank
AU - Vandermeer, Franciscus
AU - Neef, Cees
AU - van Kuijk, Sander
AU - Christiaans, Maarten H. L.
N1 - Funding Information:
We would like to thank Dr. Nas Undre from Astellas Pharma for kindly providing us the raw data of the pharmacokinetic trial as published by Saint Marcoux et al. [14]. Dr. Undre nor Astellas was otherwise involved in our study. We would also like to thank our trial nurse, Mrs. Monique Mullens, and the nurse practitioners Mr. John Dackus and Mr. Philip Ulrichts for taking the blood samples during the trials that involved patients from our centre.
Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/2/4
Y1 - 2020/2/4
N2 - Purpose Tacrolimus has a narrow therapeutic window. Measuring trough level (C-0) as surrogate for drug exposure (AUC) in renal transplant recipients has limitations. Therefore, limited sampling strategies (LSS's) have been developed. For the newer modified release, once-daily formulation (Tac QD) LSS's are based on either linear regression analysis (LRA) or population pharmacokinetics with maximum a posteriori Bayesian (MAPB) estimation. The predictive performances of both methods were compared, also to LSS's as described in literature. Methods LSS's (maximally three sampling time points) were developed for Tac QD from full 24-h sampling by LRA in 27 Caucasian, stable renal transplant recipients. Performance for accuracy (mean absolute prediction error <10%) and precision (root mean squared error <15%) was quantified also after MAPB estimation in two independent groups (early and late post-transplant, n = 12 each). Results LRA determined a single 8 hours post-dose measurement (C-8) to fulfil predefined criteria for accuracy (MAPE 3.41%) and precision (RMSE 4.28%). The best LSS contained C-2, C-8 and C-12 for the stable (MAPE 2.42%, RMSE 3.1%) and the early post-transplant group (MAPE 2.46%, RMSE 3.14%). LRA did not include C-0 for any LSS, unless it was forced into the model. MAPB estimation showed similar performance. Conclusions In renal transplant patients, sampling in the elimination phase (C-8) accurately predicted Tac QD exposure, contrary to C-0. The 3-point sampling C-2,C- C-8 and C-12 had the best performance and is also valid early post-transplant. These LSS's were similarly predictive with MAPB estimation. Dried blood spot could facilitate late sampling in clinical practice.
AB - Purpose Tacrolimus has a narrow therapeutic window. Measuring trough level (C-0) as surrogate for drug exposure (AUC) in renal transplant recipients has limitations. Therefore, limited sampling strategies (LSS's) have been developed. For the newer modified release, once-daily formulation (Tac QD) LSS's are based on either linear regression analysis (LRA) or population pharmacokinetics with maximum a posteriori Bayesian (MAPB) estimation. The predictive performances of both methods were compared, also to LSS's as described in literature. Methods LSS's (maximally three sampling time points) were developed for Tac QD from full 24-h sampling by LRA in 27 Caucasian, stable renal transplant recipients. Performance for accuracy (mean absolute prediction error <10%) and precision (root mean squared error <15%) was quantified also after MAPB estimation in two independent groups (early and late post-transplant, n = 12 each). Results LRA determined a single 8 hours post-dose measurement (C-8) to fulfil predefined criteria for accuracy (MAPE 3.41%) and precision (RMSE 4.28%). The best LSS contained C-2, C-8 and C-12 for the stable (MAPE 2.42%, RMSE 3.1%) and the early post-transplant group (MAPE 2.46%, RMSE 3.14%). LRA did not include C-0 for any LSS, unless it was forced into the model. MAPB estimation showed similar performance. Conclusions In renal transplant patients, sampling in the elimination phase (C-8) accurately predicted Tac QD exposure, contrary to C-0. The 3-point sampling C-2,C- C-8 and C-12 had the best performance and is also valid early post-transplant. These LSS's were similarly predictive with MAPB estimation. Dried blood spot could facilitate late sampling in clinical practice.
KW - Tacrolimus
KW - Kidney transplantation
KW - Pharmacokinetics
KW - Limited sampling strategy
KW - Therapeutic drug monitoring
KW - PROGRAF-BASED REGIMEN
KW - CONVERSION
KW - FORMULATIONS
KW - CURVE
KW - AREA
U2 - 10.1007/s00228-019-02814-x
DO - 10.1007/s00228-019-02814-x
M3 - Article
C2 - 32020321
SN - 0031-6970
VL - 76
SP - 685
EP - 693
JO - European Journal of Clinical Pharmacology
JF - European Journal of Clinical Pharmacology
IS - 5
ER -