Official Title: “A Prospective Observational Study of Plasma Voriconazole Concentration Measurement and Its Correlation With CYP2C19 Genotype in Korean Patients”

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.

Study Type: Observational

Study Design: Case-Only, Prospective

Study Primary Completion Date: April 2009

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.

Arms, Groups and Cohorts in this Clinical Trial

• : 1
  • 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.

Primary Measures

• To regular setting of voriconazole TDM & establish relationship with efficacy and safety
  • Time Frame: Prospective
    Safety Issue?: Yes

Secondary Measures

• To apply population pharmacokinetic-pharmacodynamic modeling and simulation technique on the clinical research of antifungal drugs.
  • Time Frame: Prospective
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 15 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: The Catholic University of Korea

Overall Clinical Trial Officials and Contacts

Dong-Gun Lee, M.D., Ph.D. Principal Investigator St. Mary's Hospital, The Catholic Univ. of Korea  

Overall Contact: Dong-Gun Lee, M.D., Ph.D. 82-2-3779-1114 symonlee@catholic.ac.kr

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00673348

Study ID Number: VCZ_TDM_Korea

ClinicalTrials.gov Identifier: NCT00673348

Health Authority: South Korea: Institutional Review Board