Population Pharmacokinetic Modeling of Intravenous Fluconazole to Inform eGFR-Based Dosing: A Simulation Study Demonstrating Superiority over Standard Regimens.

Aim: This study aimed to develop a population pharmacokinetic (PK) model of intravenous fluconazole and, using model-based simulations, propose initial dosing recommendations that optimize efficacy while limiting toxicity.

Methods

Therapeutic drug monitoring data from 116 adult patients (183 serum concentrations) treated with intravenous fluconazole between 2022 and 2025 at a single center were analyzed using nonlinear mixed-effects modeling. Monte Carlo simulations were applied to identify dosing strategies that maximize the probability of achieving the PK/PD efficacy target.

Results

Estimated glomerular filtration rate (eGFR) was the strongest predictor of fluconazole clearance, and adjusted body weight (ABW) influenced the volume of distribution. For a patient with ABW of 75 kg and eGFR of 90 mL/min, the estimated volume of distribution and clearance were 41.6 L and 0.81 L/h, respectively. An eGFR-based dosing nomogram was developed, and simulations demonstrated that this approach outperformed standard dosing regimens in achieving the PK/PD target.

Conclusions

These findings suggest an initial loading dose (2.8 times the maintenance dose) followed by individualized, eGFR-guided maintenance dosing to enhance the safety and efficacy of intravenous fluconazole therapy; however, prospective clinical validation is required before routine clinical implementation.