Table 1_Population pharmacokinetic modeling of tacrolimus using real-world data for precision dosing in pediatric liver transplant recipients younger than 36 months during the immediate postoperative period.docx

Forward predictive performance was also evaluated by forecasting the trough concentration at the next occasion using covariates alone or in combination with one or two preceding trough measurements.</p>Results<p>A total of 731 tacrolimus concentrations from 92 patients were analyzed. A one-compartment model with first-order absorption adequately described the data. Clearance decreased with increasing total bilirubin and aspartate aminotransferase, whereas volume of distribution increased with age.

Inter-occasion variability in clearance varied across the postoperative course, from a coefficient of variation of 123.8% on postoperative day (POD) 2%–10.7% on POD 5–6, before increasing to 38.8% on POD 9–11. Monte Carlo simulation placed 89.2% of observed concentrations within the 90% prediction interval. Moreover, incorporating one preceding trough reduced the mean absolute error of next-occasion predictions by approximately one-fifth, while incorporating two preceding troughs reduced it by approximately one-third, according to the performance validation.</p>Conclusion<p>Tacrolimus clearance in pediatric liver transplant recipients younger than 36 months is characterized by substantial occasion-specific variability during the immediate postoperative period, consistent with dynamic changes in graft function.

Dose individualization should therefore incorporate occasion-specific therapeutic drug monitoring data. The developed model provides a quantitative framework for MIPD, implemented here through a publicly accessible web application (smjlab.shinyapps.io/fk506_frontiers/).</p>