Voriconazole Trough Plasma Levels : Genetic Polymorphism, Efficacy, Safety in Patients With Hematologic Malignancy

The Correlation of Voriconazole Trough Plasma Levels With Genetic Polymorphism, Efficacy, and Safety Outcomes in Hematologic Malignancy Patients With Invasive Pulmonary Aspergillosis

Multiple factors are associated with a large variability in voriconazole exposure following standard dose administration, such as non-linear saturable pharmacokinetics, drug-drug interactions, liver disease, patient age, and genetic polymorphism of the metabolic enzymes.

Voriconazole is extensively metabolized by the human hepatic enzymes, primarily mediated by CYP2C19. The polymorphisms account for a relatively large portion of inter-individual variance observed in voriconazole plasma concentrations.

However, there are limited data on the relationships between voriconazole blood levels and clinical outcomes or safety in Asian populations.

The purpose of this study is to investigate the relationships of voriconazole blood levels with genetic polymorphism, safety, and clinical outcomes in immunocompromised patients with invasive pulmonary aspergillosis.

The investigators are trying to establish that routine clinical practice for voriconazole therapeutic drug monitoring can improve the efficacy and safety outcomes.

In Korean patients with hematologic malignancy, the investigators also want to propose the optimal dosing guideline of voriconazole with different genetic polymorphisms.

Inclusion Criteria: all items below

• male or female ≥ 15 years of age
• immunocompromised patients with hematologic disorders
• patients received voriconazole due to treat proven, probable invasive (pulmonary) aspergillosis

Exclusion Criteria:

• severe hepatic dysfunction (t.bil, AST, ALT, ALP > 5 x upper normal limit)
• who experienced hypersensitivity to azoles
• pregnant women