Tissue Pharmacokinetics of Antifungal Drugs: A Review.

Invasive fungal infections are a major cause of morbidity and mortality in immunocompromised and critically ill patients. While plasma pharmacokinetics (PK) commonly guide antifungal dosing, they may not reliably reflect drug exposure at infection sites, particularly in compartments that are difficult to reach. Tissue PK is increasingly recognized as an important determinant of optimal dosing and therapeutic success. This review summarizes available clinical data on tissue PK of approved antifungal agents, including triazoles, echinocandins, amphotericin B formulations, and flucytosine. Studies were identified via a PubMed search through July 2025, focusing on prospective human trials reporting both plasma and tissue concentrations. Our findings revealed marked variability in tissue penetration across drugs and compartments. These findings underscore the limitations of relying solely on plasma concentrations to estimate tissue exposure and emphasize the importance of considering tissue penetration when selecting and dosing antifungal therapy.