Therapeutic Drug Monitoring (TDM) of Voriconazole and Correlation With CYP2C19 Genotype in Korean Populations

The Catholic University of Korea

Status: Unknown

Conditions: Neutropenia; Mycoses; Bone Marrow Transplantation

Study type: Observational

Funder types: Other

Identifiers

NCT00673348

VCZ_TDM_Korea

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 15 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

40 participants in 1 patient group

1

Description:

Patients suspected of invasive fungal infection (proven or probable cases) with immunocompromised state (for example, during neutropenia, receiving HSCT) in Catholic Hematopoietic Stem Cell Transplantation \[HSCT\] Center in Seoul, Korea.