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

Neutropenia Clinical Trial

Official title:

A Prospective Observational Study of Plasma Voriconazole Concentration Measurement and Its Correlation With CYP2C19 Genotype in Korean Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00673348
• Other study ID #: VCZ_TDM_Korea
• Status: Recruiting
• Phase: N/A
• First received: May 5, 2008
• Last updated: July 22, 2008
• Start date: May 2008
• Est. completion date: April 2010

Study information

• Verified date: June 2008
• Source: The Catholic University of Korea
• Contact: Dong-Gun Lee, M.D., Ph.D.
• Phone: 82-2-3779-1114
• Email: symonlee[@]catholic.ac.kr
• Is FDA regulated: No
• Health authority: South Korea: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 2010
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 65 Years

Eligibility

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

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Bone Marrow Transplantation
• Mycoses
• Neutropenia

Locations

Country	Name	City	State
Korea, Republic of	St. Mary's Hospital	Seoul
Korea, Republic of	St. Mary's Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
The Catholic University of Korea

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To regular setting of voriconazole TDM & establish relationship with efficacy and safety		Prospective	Yes
Secondary	To apply population pharmacokinetic-pharmacodynamic modeling and simulation technique on the clinical research of antifungal drugs.		Prospective	No