Current Evidence on Voriconazole Exposure and Individualized Therapy for Aspergillosis

Abstract: With emerging global antifungal resistance, voriconazole is a preferred first-line antifungal agent for the treatment of aspergillosis, and therapeutic drug monitoring (TDM) is frequently utilized during therapy. This review examines evidence from international guidelines, clinical studies, case reports, and population pharmacokinetic analyses to investigate the multifactorial drivers influencing voriconazole therapy. Current guidelines demonstrate variability in recommended target trough concentrations, though a range of 1.0– 5.5 mg/L appears as a frequently cited reference interval; however, these recommendations are often derived from heterogeneous populations rather than being specific to aspergillosis. Plasma voriconazole concentration alone may not fully account for the variability in clinical outcomes. Efficacy and safety are influenced by multiple factors, including CYP2C19 polymorphisms, disease severity, host immune status, and infection site. Consequently, the interpretation of a single concentration threshold may be limited. A multidimensional approach—considering genotype, host factors, inflammatory status, and dynamic clinical context—is a component of individualized therapy for characterizing treatment response and toxicity risk. Within this framework, TDM is an established tool for assessing systemic exposure, and its integration with clinical and biological information is relevant for clinical assessment. Altogether, these observations underscore the value of integrated clinical assessment while identifying remaining evidence gaps for further investigation. Keywords: voriconazole, Aspergillus , therapeutic drug monitoring, individualized dosing, pharmacokinetics