Pharmacokinetics of Antifungal Agents in Clinical Settings

Antifungal pharmacokinetics encompasses the absorption, distribution, metabolism and excretion of agents used to treat invasive fungal infections. Key drug classes include polyenes (for example amphotericin B), azoles (fluconazole, voriconazole, posaconazole, isavuconazole), echinocandins (caspofungin, micafungin, anidulafungin) and antimetabolites (flucytosine). Each class exhibits distinct protein binding, tissue penetration and metabolic pathways, with azoles notably subject to cytochrome P450 interactions and echinocandins undergoing non-CYP hepatic clearance. Clinical pharmacokinetics must account for patient factors such as critical illness, organ dysfunction, body weight, extracorporeal support and paediatric status. Attainment of pharmacokinetic/pharmacodynamic targets (for example fAUC/MIC thresholds) is closely linked to therapeutic success and minimisation of resistance. Therapeutic drug monitoring and population modelling increasingly guide personalised dosing to optimise efficacy, safety and global stewardship of antifungal therapy.

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Pharmacokinetics of Antifungal Agents in Clinical Settings publication trend

The graph below shows the total number of articles in pharmacokinetics of antifungal agents in clinical settings across all publications each year (not limited to Nature Index journals).

Technical terms

Area under the concentration–time curve (AUC): Integral of drug concentration over time representing total systemic exposure.

fAUC/MIC: Ratio of free drug AUC to minimum inhibitory concentration; principal pharmacodynamic index for azoles.

Population pharmacokinetics (popPK): Modelling approach that characterises variability in drug concentrations across a patient population.

Therapeutic drug monitoring (TDM): Measurement of plasma drug levels to individualise dosing and ensure target attainment.

Target-site penetration: Extent to which an antifungal reaches the infected tissue compartment, critical for deep-seated infections.

References

1. Critical appraisal beyond clinical guidelines for intraabdominal candidiasis. Critical Care (2023).
2. Fluconazole Dosing for the Prevention of Candida spp. Infections in Hemato-Oncologic Pediatric Patients: Population Pharmacokinetic Modeling and Probability of Target Attainment Simulations. Pharmaceutics (2025).
3. Evaluating cardiac disorders associated with triazole antifungal agents based on the US Food and Drug Administration Adverse Event reporting system database. Frontiers in Pharmacology (2024).
4. Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients. Infection (2017).