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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Patients with hematologic malignancies who were given voriconazole to treat invasive (pulmonary) aspergillosis at Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| voriconazole | Drug | intravenous, oral administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| Successful outcome at 12 weeks after voriconazole use | Successful outcome = complete response + partial response Unsuccessful outcome = stable disease + failure of therapy + indeterminate response | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| IFI (invasive fungal infection)-related mortality at 12 weeks | IFI (invasive fungal infection)-related mortality at 12 weeks | 12 weeks |
| Successful outcomes at various time points | Successful outcomes at 1 week,2 weeks,4 weeks, and 8 weeks after voriconazole use |
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Inclusion Criteria: all items below
Exclusion Criteria:
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Patients with hematologic malignancies who were given voriconazole to treat invasive (pulmonary) aspergillosis at Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asan Medical Center, University of Ulsan College of Medicine | Seoul | 138-736 | South Korea |
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| ID | Term |
|---|---|
| D000072742 | Invasive Fungal Infections |
| D055744 | Invasive Pulmonary Aspergillosis |
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D009181 | Mycoses |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D055732 | Pulmonary Aspergillosis |
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| ID | Term |
|---|---|
| D065819 | Voriconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| 1 week, 2 weeks, 4 weeks, and 8 weeks |
| Non-IFI (invasive fungal infection)-related mortality at 12 weeks | Non-IFI (invasive fungal infection)-related mortality at 12 weeks | 12 weeks |
| breakthrough IFI | breakthrough IFI | 12 weeks |
| Adverse drug reactions | Adverse drug reactions (liver function test impairment, visual disturbance, hallucination, photosensitive rash, renal impairment) | 12 weeks |
| D001228 |
| Aspergillosis |
| D008172 | Lung Diseases, Fungal |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |