Therapeutic Drug Monitoring (TDM) of Voriconazole and Correlation With CYP2C19 Genotype in Korean Populations
Recruitment status was Recruiting
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 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|
- To regular setting of voriconazole TDM & establish relationship with efficacy and safety [ Time Frame: Prospective ] [ Designated as safety issue: Yes ]
- To apply population pharmacokinetic-pharmacodynamic modeling and simulation technique on the clinical research of antifungal drugs. [ Time Frame: Prospective ] [ Designated as safety issue: No ]
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.
|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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00673348
|Contact: Dong-Gun Lee, M.D., Ph.D.||82-2-3779-1114 ext firstname.lastname@example.org|
|Contact: Dong-Seok Yim, M.D., Ph.D.||82-2-590-1114 ext email@example.com|
|Korea, Republic of|
|St. Mary's Hospital||Not yet recruiting|
|Seoul, Korea, Republic of, 150-713|
|Contact: Dong-Gun Lee, M.D., Ph.D. 82-2-3779-1114 ext 1099 firstname.lastname@example.org|
|Principal Investigator: Dong-Gun Lee, M.D., Ph.D.|
|St. Mary's Hospital||Recruiting|
|Seoul, Korea, Republic of, 150-713|
|Contact: Hae-Young Youn, Pharm D 82-2-3779-1114 ext 1216 email@example.com|
|Principal Investigator:||Dong-Gun Lee, M.D., Ph.D.||St. Mary's Hospital, The Catholic Univ. of Korea|