TY - JOUR
T1 - Model-Based Tacrolimus Follow-up Dosing in Adult Renal Transplant Recipients
T2 - A Simulation Trial
AU - Francke, Marith I.
AU - Hesselink, Dennis A.
AU - Andrews, Louise M.
AU - van Gelder, Teun
AU - Keizer, Ron J.
AU - de Winter, Brenda C.M.
N1 - Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/10
Y1 - 2022/10
N2 - BACKGROUND: Initial algorithm-based dosing appears to be effective in predicting tacrolimus dose requirement. However, achieving and maintaining the target concentrations is challenging. Model-based follow-up dosing, which considers patient characteristics and pharmacological data, may further personalize treatment. This study investigated whether model-based follow-up dosing could lead to more accurate tacrolimus exposure than standard therapeutic drug monitoring (TDM) in kidney transplant recipients after an initial algorithm-based dose. METHODS: This simulation trial included patients from a prospective trial that received an algorithm-based tacrolimus starting dose followed by TDM. For every measured tacrolimus predose concentration (C0,obs), model-based dosing advice was simulated using the InsightRX software. Based on previous tacrolimus doses and C0 , age, body surface area, CYP3A4 and CYP3A5 genotypes, hematocrit, albumin, and creatinine, the optimal next dose, and corresponding tacrolimus concentration (C0,pred ) were predicted. RESULTS: Of 190 tacrolimus C0 values measured in 59 patients, 121 (63.7%; 95% CI 56.8-70.5) C0,obs were within the therapeutic range (7.5-12.5 ng/mL) versus 126 (66.3%, 95% CI 59.6-73.0) for C0,pred ( P = 0.89). The median absolute difference between the tacrolimus C0 and the target tacrolimus concentration (10.0 ng/mL) was 1.9 ng/mL for C0,obs versus 1.6 ng/mL for C0,pred . In a historical cohort of 114 kidney transplant recipients who received a body weight-based starting dose followed by TDM, 172 of 335 tacrolimus C0 (51.3%) were within the therapeutic range (10.0-15.0 ng/mL). CONCLUSIONS: The combination of an algorithm-based tacrolimus starting dose with model-based follow-up dosing has the potential to minimize under- and overexposure to tacrolimus in the early posttransplant phase, although the additional effect of model-based follow-up dosing on initial algorithm-based dosing seems small.
AB - BACKGROUND: Initial algorithm-based dosing appears to be effective in predicting tacrolimus dose requirement. However, achieving and maintaining the target concentrations is challenging. Model-based follow-up dosing, which considers patient characteristics and pharmacological data, may further personalize treatment. This study investigated whether model-based follow-up dosing could lead to more accurate tacrolimus exposure than standard therapeutic drug monitoring (TDM) in kidney transplant recipients after an initial algorithm-based dose. METHODS: This simulation trial included patients from a prospective trial that received an algorithm-based tacrolimus starting dose followed by TDM. For every measured tacrolimus predose concentration (C0,obs), model-based dosing advice was simulated using the InsightRX software. Based on previous tacrolimus doses and C0 , age, body surface area, CYP3A4 and CYP3A5 genotypes, hematocrit, albumin, and creatinine, the optimal next dose, and corresponding tacrolimus concentration (C0,pred ) were predicted. RESULTS: Of 190 tacrolimus C0 values measured in 59 patients, 121 (63.7%; 95% CI 56.8-70.5) C0,obs were within the therapeutic range (7.5-12.5 ng/mL) versus 126 (66.3%, 95% CI 59.6-73.0) for C0,pred ( P = 0.89). The median absolute difference between the tacrolimus C0 and the target tacrolimus concentration (10.0 ng/mL) was 1.9 ng/mL for C0,obs versus 1.6 ng/mL for C0,pred . In a historical cohort of 114 kidney transplant recipients who received a body weight-based starting dose followed by TDM, 172 of 335 tacrolimus C0 (51.3%) were within the therapeutic range (10.0-15.0 ng/mL). CONCLUSIONS: The combination of an algorithm-based tacrolimus starting dose with model-based follow-up dosing has the potential to minimize under- and overexposure to tacrolimus in the early posttransplant phase, although the additional effect of model-based follow-up dosing on initial algorithm-based dosing seems small.
UR - https://www.scopus.com/pages/publications/85138446640
U2 - 10.1097/FTD.0000000000000979
DO - 10.1097/FTD.0000000000000979
M3 - Article
C2 - 35344525
AN - SCOPUS:85138446640
SN - 0163-4356
VL - 44
SP - 606
EP - 614
JO - Therapeutic Drug Monitoring
JF - Therapeutic Drug Monitoring
IS - 5
ER -