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.