Optimization of voriconazole dosage via population pharmacokinetic analysis based on the albumin–bilirubin (ALBI) score of patients with liver dysfunction

Abstract

Introduction

Voriconazole (VRCZ) is an antifungal agent used to treat refractory fungal infections. Its dosage is adjusted based on the individual liver function. In this study, we aimed to establish a population pharmacokinetic analysis model based on the albumin–bilirubin (ALBI) score to objectively assess the liver function using only albumin and total bilirubin levels as covariates.

Methods

In total, 126 plasma samples of 16 patients with liver dysfunction who received oral VRCZ between 2012 and 2022 were analyzed in this study. Phoenix NLME software was used for population pharmacokinetic analysis, and Monte Carlo simulations were performed to determine the optimal dosing regimen to achieve the target blood VRCZ concentration.

Results

Blood VRCZ concentration was described using a one-compartment model with lag time. In the final model, objective function was significantly decreased upon ALBI score incorporation into clearance. Monte Carlo simulations showed that the optimal dosing schedules were 100 mg twice daily, 75 mg twice daily, and 50 mg twice daily for ALBI scores of −3, −2, and −1, respectively. Notably, for an ALBI score of 0, target blood VRCZ concentration was exceeded, even a dosing regimen of 50 mg twice daily.

Conclusion

To the best of our knowledge, this study is the first to incorporate the ALBI score into a population pharmacokinetic model for VRCZ. Our simulation results suggest that the maintenance dose should be reduced based on the ALBI score. Furthermore, our findings highlight the potential use of the ALBI score for optimal drug dosage design.