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

• Conditions: Bone Marrow Transplantation; Mycoses; Neutropenia

• Registration Number: NCT00673348
• Lead Sponsor: The Catholic University of Korea

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.

Study Timeline

• Study Start: 2008-05
• Study First Submitted: 2008-05-05
• Study First Submitted QC: 2008-05-06
• Study First Posted: 2008-05-07
• Status Verified: 2008-06
• Last Update Submitted: 2008-07-22
• Last Update Posted: 2008-07-24
• Primary Completion: 2009-04
• Study Completion: 2010-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To regular setting of voriconazole TDM & establish relationship with efficacy and safety	Prospective

Secondary Outcome Measures

Name	Time	Method
To apply population pharmacokinetic-pharmacodynamic modeling and simulation technique on the clinical research of antifungal drugs.	Prospective

Trial Locations

Locations (1)

St. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of