Voriconazole Blood Level and Liver Metabolizing Enzyme in Taiwanese Patients
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|ClinicalTrials.gov Identifier: NCT00745992|
Recruitment Status : Unknown
Verified September 2008 by National Taiwan University Hospital.
Recruitment status was: Not yet recruiting
First Posted : September 3, 2008
Last Update Posted : September 3, 2008
Voriconazole is an effective antifungal agent and may decrease morbidity and mortality for patients with invasive fungal infections. It is metabolized via liver enzymes. However, these enzymes exhibit different activities in individual patient (genetic polymorphism). Higher proportions of Asians metabolize voriconazole slower than Caucasians and African Americans do. Slower metabolizers may experience dose-associated adverse events more frequently, such as visual disturbances, liver function test abnormalities, and neurological complications. On the other hand, extensive metabolizer or other physiologic conditions may lead to lower blood levels of voriconazole, which may result in treatment failure.
We plan to enroll patient who take voriconazole and examine their liver enzyme activities and blood samples for peak and trough drug levels. We will collect potential factors affecting voriconazole levels, and correlate the levels with the dosing regimen, activity of liver enzyme, occurrence of adverse events, and treatment outcomes. The goal of this study is to determine if monitoring of voriconazole blood levels is necessary in Taiwan.
|Condition or disease||Intervention/treatment|
|Invasive Fungal Infections||Other: Blood drawn (lab data)|
The incidence of opportunistic, invasive fungal infections has dramatically increased over the past two decades and they cause high morbidity and mortality in a variety of patient populations. Voriconazole, a triazole antifungal agent, has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability and wide tissue distribution. Voriconazole is extensively metabolized by the hepatic cytochrome P450 isoenzymes, CYP 2C19, CYP 2C9 and CYP 3A4. The affinity of voriconazole is greatest for isoenzyme CYP 2C19 which exhibits genetic polymorphism with 15-20% of Asian populations being poor/slow metabolizers, whereas the prevalence is much lower (3-5%) amongst Caucasians and African Americans. Studies conducted in Caucasian and Japanese healthy subjects have demonstrated that poor metabolizers have, on average, four times higher voriconazole AUC than homozygous extensive metabolisers, while the AUC of heterozygous extensive metabolizers is two times higher than that of homozygous extensive metabolizers. The most commonly reported adverse events associated with voriconazole use include visual disturbances, liver function test abnormalities, and neurological complications. All of them have been reported to be associated with higher plasma concentrations and / or doses. In term of efficacy, an analysis showed a trend toward worse outcomes in patients with voriconazole plasma concentrations < 0.5 μg/mL although this remains controversial. Since Asians have more CYP 2C19 polymorphism, we expect to see more patients with a wider range of voriconazole plasma concentrations than in previous studies in Caucasian patients. Our study will likely provide stronger evidence in explanation of the relationship between voriconazole plasma concentrations and clinical observations.
We plan to enroll patient who take voriconazole and examine their CYP 2C19 genotypes and plasma samples for peak and trough concentrations. We will collect potential confounding factors affecting voriconazole plasma concentrations, and correlate the concentrations with the dosing regimen, presence or absence of CYP 2C19 polymorphism, occurrence of adverse events, and treatment outcomes. The result of this study will be beneficial in clarify the international debate on controversial issue in the voriconazole plasma concentration monitoring. The ultimate goals of this study is to determine if monitoring of voriconazole plasma concentrations is desired in select patient populations or under certain circumstances in Taiwan.
|Study Type :||Observational|
|Estimated Enrollment :||200 participants|
|Official Title:||Voriconazole Therapeutic Drug Monitoring and CYP2C19 Genetic Polymorphisms in Taiwanese Patients|
|Study Start Date :||October 2008|
|Estimated Primary Completion Date :||July 2011|
|Estimated Study Completion Date :||July 2011|
Other: Blood drawn (lab data)
- Relationship between treatment outcome and voriconazole plasma levels [ Time Frame: continuous observation through treatment course ]
- Relationship between voriconazole plasma levels and CYP2C19 polymorphism [ Time Frame: 3-5 days after start of IV/PO voriconazole ]
- Relationship between safety and voriconazole plasma levels [ Time Frame: Continuous observation through treatment course ]
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00745992
|Contact: Shu-Wen Lin, PharmD, MS||886-2-2312-3456 ext email@example.com|
|Contact: Fe-Lin L. Wu, Ph.D.||886-2-2312-3456 ext firstname.lastname@example.org|
|National Taiwan University Hospital||Not yet recruiting|
|Taipei, Taiwan, 100|
|Contact: Shu-Wen Lin, PharmD, MS 886-2-2312-3456 ext 88408 email@example.com|
|Contact: Fe-Lin L. Wu, Ph.D. 886-2-2312-3456 ext 88389 firstname.lastname@example.org|
|Principal Investigator: Shu-Wen Lin, PharmD, MS|
|Sub-Investigator: Fe-Lin L. Wu, Ph.D.|
|Principal Investigator:||Shu-Wen Lin, PharmD, MS||Graduate Institute of Clinical Pharmacy, National Taiwan University|