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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified June 2008 by The Catholic University of Korea.
Recruitment status was:  Recruiting
Information provided by:
The Catholic University of Korea Identifier:
First received: May 5, 2008
Last updated: July 22, 2008
Last verified: June 2008
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.

Bone Marrow Transplantation

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: A Prospective Observational Study of Plasma Voriconazole Concentration Measurement and Its Correlation With CYP2C19 Genotype in Korean Patients

Resource links provided by NLM:

Further study details as provided by The Catholic University of Korea:

Primary Outcome Measures:
  • To regular setting of voriconazole TDM & establish relationship with efficacy and safety [ Time Frame: Prospective ]

Secondary Outcome Measures:
  • To apply population pharmacokinetic-pharmacodynamic modeling and simulation technique on the clinical research of antifungal drugs. [ Time Frame: Prospective ]

Biospecimen Retention:   Samples With DNA
  • Two times of venous blood sampling will be carried out at steady state. Three ml of venous blood is sampled right before the morning dose (trough sampling). The second sampling is carried out at any time point within 2-4 hours after the morning dose (peak sampling). To obtain the exact dose and sampling history, at least three dosing times around the trough and peak sampling will be recorded to the minute. Sampling time will also be recorded as clock time.
  • Genotyping of CYP2C19 will also be performed using 3 ml of peripheral blood sampled into EDTA tubes.

Estimated Enrollment: 40
Study Start Date: May 2008
Estimated Study Completion Date: April 2010
Estimated Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
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.

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.

Ages Eligible for Study:   15 Years to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
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.

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00673348

Korea, Republic of
St. Mary's Hospital
Seoul, Korea, Republic of, 150-713
Sponsors and Collaborators
The Catholic University of Korea
Principal Investigator: Dong-Gun Lee, M.D., Ph.D. St. Mary's Hospital, The Catholic Univ. of Korea
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Dong-Gun Lee / Assistant Professor, Division of Infectious Diseases, Department of Internal Medicine Identifier: NCT00673348     History of Changes
Other Study ID Numbers: VCZ_TDM_Korea 
Study First Received: May 5, 2008
Last Updated: July 22, 2008

Keywords provided by The Catholic University of Korea:

Additional relevant MeSH terms:
Leukocyte Disorders
Hematologic Diseases
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors processed this record on February 20, 2017