Bone Marrow Transplantation, Mycoses, Neutropenia
Conditions
Keywords
Mycoses, Voriconazole
Brief summary
Voriconazole (VCZ), the antifungal drug active against Candida and Aspergillus is a substrate of CYP2C19, whose proportion of poor metabolizers is about \ 20% in Asian population. The AUC's of VCZ differs over 4 folds by CYP2C19 genotypes of homozygotic wild type, heterozygote, and homozygotic poor metabolizers. The Asian population enrolled in the metabolism of VCZ were mainly Japanese and Chinese, without Korean subjects. The proportion of poor metabolizers in Korean population is known to be around 12% (Pharmacogenetics. 1996 Dec;6(6):547-51). The importance of CYP2C19 genotypes on the pharmacokinetics (PK) of voriconazole is well established, Hence, it is desirable to individualize the dosage regimen of VCZ according to the genotypes of patients. Fungal infection in immunocompromised patients is a life threatening condition which needs critical care. Although the PK change by genotypes are well known, its clinical implication or need for different dosage regimen by genotypes is not established, yet.
Detailed description
The investigators are trying to set up voriconazole (VCZ) therapeutic drug monitoring (TDM) & establish relationship with efficacy and safety in Korea. The investigators also want to propose the optimal dosage regimen for VCZ over different genotypes of CYP2C19 in the immunocompromised patients in Korea.
Interventions
None listed
Sponsors
The Catholic University of Korea
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
15 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Immunocompromised adults who are treated with voriconazole due to proven or probable invasive fungal infections
Exclusion criteria
* Patients who have been treated with other investigational drugs * Patients with liver dysfunction (aminotransferase level ≥ 5 times the upper limit of normal, bilirubin or alkaline phosphatase level \> 3 times the upper limit of normal) * Patients with renal dysfunction (Cr level \> 2.5 times the upper limit of normal) * Pregnant women * Patients younger than 15 years of age
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To regular setting of voriconazole TDM & establish relationship with efficacy and safety | Prospective |
Secondary
| Measure | Time frame |
|---|---|
| To apply population pharmacokinetic-pharmacodynamic modeling and simulation technique on the clinical research of antifungal drugs. | Prospective |
Countries
South Korea
Contacts
Primary ContactDong-Gun Lee, M.D., Ph.D.
Backup ContactDong-Seok Yim, M.D., Ph.D.
Outcome results
None listed