Model-Based Tacrolimus Follow-Up Dosing in Adult Renal Transplant Recipients: A Simulation Trial.

Abstract 

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 pre-dose 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 bodyweight-based starting dose followed by TDM, 172 out 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 post-transplant phase, although the additional effect of model-based follow-up dosing on initial algorithm-based dosing seems small.

Francke, M. I., Hesselink, D. A., Andrews, L. M., Van Gelder, T., Keizer, R. J., & De Winter, B. C. (2022). Model-Based Tacrolimus Follow-Up Dosing in Adult Renal Transplant Recipients: A Simulation Trial. Therapeutic Drug Monitoring, 10-1097.