Voriconazole and the liver

Area of Science:

• Mycology
• Pharmacology
• Clinical Pharmacy

Background:

• Voriconazole is a vital azole antifungal for treating invasive fungal infections, particularly aspergillosis, in immunocompromised patients.
• Immunosuppressed individuals, including those undergoing chemotherapy or transplantation, are at high risk for serious fungal infections.
• Significant inter-patient variability in voriconazole serum concentrations is observed, complicating treatment and necessitating careful management.

Purpose of the Study:

• To review the factors influencing voriconazole pharmacokinetics and therapeutic drug monitoring.
• To discuss the recommended therapeutic range for voriconazole and the consequences of sub- or supra-therapeutic levels.
• To highlight the importance of monitoring voriconazole levels and clinical outcomes, despite ongoing debates on correlation with adverse effects.

Main Methods:

• Literature review of voriconazole pharmacokinetics, pharmacodynamics, and clinical studies.
• Analysis of factors contributing to voriconazole serum level variability.
• Synthesis of recommendations for therapeutic drug monitoring of voriconazole.

Main Results:

• Voriconazole pharmacokinetics are nonlinear and influenced by genetic polymorphisms (CYP2C19), organ function, and drug-drug interactions.
• Therapeutic voriconazole serum concentrations are generally recommended between 1.5 and 4 μg/mL.
• Sub-therapeutic levels reduce efficacy, while supra-therapeutic levels increase the risk of neurological and hepatic toxicity.

Conclusions:

• Therapeutic drug monitoring of voriconazole is essential for optimizing treatment outcomes in at-risk populations.
• Despite variability and lack of definitive correlation with adverse events in all cases, monitoring is advised, especially in high-risk groups.
• Further research may clarify the precise role of therapeutic drug monitoring in mitigating voriconazole-associated toxicities.