Structured Evaluation of Model-Informed Precision Dosing of Mycophenolic Acid and Tacrolimus in Pediatric Patients with Kidney Disease

Mycophenolic acid and tacrolimus are frequently used in kidney transplant recipients and patients with nephrotic syndrome. For both drugs, therapeutic drug monitoring is recommended. Model-informed precision dosing, not only uses population pharmacokinetic data but also increases flexibility. To optimize treatment with mycophenolic acid and tacrolimus using a limited number of samples, we evaluated model-informed precision dosing for both drugs. We performed the following steps: (1) selection of population pharmacokinetic models; (2) retrospective evaluation using real-world data; and (3) evaluation of limited sampling strategies, (4) prospective evaluation of the predictive performance by predicting an area under the concentration–time curve from time zero to 12 h at a next occasion (3 months later). Acceptable bias and imprecision were defined as a mean prediction error and a normalized root mean square error of less than 25%. A 3‑point sampling schedule ( t = 0, t = 1, t = 2 h) provided accurate area under the concentration–time curve from time zero to 12 h estimation for both drugs, with mean prediction error and normalized root mean square error of 0.1% (− 0.3 to 0.6%) and 21.0% (7.1–34.8%) for mycophenolic acid, and 0.2% (0.03–0.4%) and 7.8% (3.0–12.6%) for tacrolimus. Substantial between-occasion variability limited the prediction of future area under the concentration–time curve from time zero to 12 h. For mycophenolic acid, the mean prediction error was 15.4% (14.4–16.4%) and the normalized root mean square error was 48.6% (18.2–79.0%). For tacrolimus, corresponding values were 64.2% (59.7–68.7%) for mean prediction error and 210% (37.1–383%) for normalized root mean square error. Model-informed precision dosing-guided limited sampling strategies are feasible for estimation of current exposure using similar sampling times for mycophenolic acid and tacrolimus. Accurate long-term prediction is not possible, underscoring the need for repeated therapeutic drug monitoring. NCT06095895.