Population Pharmacokinetic Analysis of Everolimus Based on Albumin-Bilirubin Scores in Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVE: Several hepatic function scores, including the albumin-bilirubin (ALBI) score, have been proposed to guide everolimus dosage adjustments in kidney transplant recipients. However, whether these scoring systems can be used to individualize the everolimus dosing regimen remains unclear. Hence, in this study, we aimed to individualize the everolimus dosing schedule using population pharmacokinetic analysis. METHODS: In this retrospective study, we enrolled adult kidney transplant recipients who received oral everolimus at Mie University Hospital. The population pharmacokinetic model was a one-compartment model with first-order absorption. Covariates for apparent clearance were tested using stepwise forward and backward methods. Monte Carlo simulations were performed to predict the probability of the target everolimus trough concentration. RESULTS: The dataset included 36 patients with 861 everolimus trough concentrations [(median (range)] of [4.2 (0.6-12.9) ng/mL] and a median follow-up of 707 (7-2177) days. The median ALBI score was - 2.85 (- 3.19 to - 2.31), the median apparent clearance of everolimus was 7.96 L/h, and a significant decrease was observed at higher ALBI scores. Based on Monte Carlo simulation, patients with an ALBI score of - 2.60 required an everolimus dose of 0.5 mg and 0.75 mg twice daily to achieve the therapeutic range (3.0-8.0 ng/mL), whereas those with an ALBI score of - 1.39 required 0.5 mg twice daily. CONCLUSIONS: The population pharmacokinetic model provided a dosing regimen for everolimus based on the ALBI score.