Unraveling the impact of renal impairment and renal replacement therapy modalities on fluconazole pharmacokinetics.

BACKGROUND

Fluconazole is a triazole antifungal agent predominantly eliminated by renal excretion, making its pharmacokinetics (PK) highly susceptible to changes in renal function.

PURPOSE: This study aimed to systematically investigate how varying degrees of renal impairment and the use of renal replacement therapy (RRT) modalities-including continuous veno-venous hemofiltration (CVVHF), hemodiafiltration (CVVHDF), and peritoneal dialysis (PD)-alter the PK behavior of fluconazole. By quantitatively comparing key PK parameters across healthy individuals, critically ill patients, and those undergoing RRT, this review seeks to establish evidence-based recommendations for individualized dosing strategies that optimize efficacy while minimizing toxicity.

METHODS

A structured literature review was conducted using electronic databases to identify original human studies reporting key PK parameters of fluconazole, including area under the curve (AUC), maximum plasma concentration (Cmax), clearance (CL), volume of distribution (Vd), and elimination half-life (T½). Data were extracted and standardized for inter-group comparisons under equivalent dosing and administration conditions.

RESULTS

The analysis revealed that fluconazole PK remain linear in healthy individuals but demonstrate nonlinearity in critically ill and renally impaired patients. In RRT recipients, AUC values varied by as much as 2.27-fold and T½ by up to 3.37-fold compared to healthy controls. CL was substantially reduced (5.47-fold) in patients with severe renal dysfunction and elevated (2.50-fold) in those receiving CVVHDF. These differences were influenced not only by renal function but also by dialysis modality, dialysate flow rates, and filter characteristics.

CONCLUSION

These findings underscore the need for individualized fluconazole dosing strategies tailored to renal function and dialysis parameters. Recognizing the PK alterations across patient groups can optimize antifungal efficacy while minimizing toxicity, supporting the rationale for dose adjustments based on clinical and physiological contexts.