Aims: Pharmacokinetics of tacrolimus after sublingual administration is not characterized in paediatric liver transplant patients. Therefore, we aimed to develop a population pharmacokinetic model of sublingually administered tacrolimus in patients who cannot swallow the capsules due to their age, sedation status and/or mechanical ventilation during the first weeks post-transplantation. Methods: Demographic, clinical and pharmacological variables, including tacrolimus whole blood concentrations obtained from therapeutic drug monitoring and data from dense-sampling pharmacokinetic profiles, were recorded in 26 paediatric patients with biliary atresia who underwent liver transplantation between 2016 and 2021. Population pharmacokinetic analysis was performed with NONMEM v7.4. Results: Disposition of tacrolimus was best characterized by a 2-compartment model with clearance achieving half of the maximum elimination capacity (CL MAX = 4.1 L/h) at 4.6 days post-transplantation (T 50 ). Compared to sedated patients, nonsedated status showed an increased first-order absorption rate constant (1.1 vs. 0.1 h À1 ) and a 24% reduction in bioavailability (F NS ) at 14 days post-transplant. The model was ableThe authors confirm that the Principal Investigator for this paper is Daniel Buamscha, MD, and that he had direct clinical responsibility for patients.

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