Therapeutic Drug Monitoring (TDM) of Voriconazole and Correlation With CYP2C19 Genotype in Korean Populations
Recruitment status was Recruiting
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Purpose
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.
| Condition |
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Mycoses Neutropenia 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 |
- 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.
| 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) |
| Groups/Cohorts |
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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.
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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.
Eligibility| Ages Eligible for Study: | 15 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
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| Contact: Dong-Gun Lee, M.D., Ph.D. | 82-2-3779-1114 ext 1099 | symonlee@catholic.ac.kr |
| Contact: Dong-Seok Yim, M.D., Ph.D. | 82-2-590-1114 ext 1201 | yimds@catholic.ac.kr |
| 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 symonlee@catholic.ac.kr | |
| 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 baram@catholic.ac.kr | |
| Principal Investigator: | Dong-Gun Lee, M.D., Ph.D. | St. Mary's Hospital, The Catholic Univ. of Korea |
More Information
No publications provided by The Catholic University of Korea
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Dong-Gun Lee / Assistant Professor, Division of Infectious Diseases, Department of Internal Medicine |
| ClinicalTrials.gov Identifier: | NCT00673348 History of Changes |
| Other Study ID Numbers: | VCZ_TDM_Korea |
| Study First Received: | May 5, 2008 |
| Last Updated: | July 22, 2008 |
| Health Authority: | South Korea: Institutional Review Board |
Keywords provided by The Catholic University of Korea:
|
Mycoses Voriconazole |
Additional relevant MeSH terms:
|
Mycoses Neutropenia Agranulocytosis Leukopenia Leukocyte Disorders Hematologic Diseases Voriconazole |
Antifungal Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions 14-alpha Demethylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 21, 2013