Clinical trial NCT00673348: Therapeutic Drug Monitoring (TDM) of Voriconazole and Correlation With CYP2C19 Genotype in Korean Populations
Official title: A Prospective Observational Study of Plasma Voriconazole Concentration Measurement and Its Correlation With CYP2C19 Genotype in Korean Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Mycoses
Neutropenia
Bone Marrow Transplantation
Keywords: Mycoses
Voriconazole
Lead sponsor: The Catholic University of Korea
Sponsor class: OTHER
First posted: 2008-05-07
Enrollment: 40
Sex: ALL
Minimum age (years): 15
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

Brief 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.

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 criteria: 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

Primary outcomes:
measure: To regular setting of voriconazole TDM & establish relationship with efficacy and safety
timeFrame: Prospective
Secondary outcomes:
measure: To apply population pharmacokinetic-pharmacodynamic modeling and simulation technique on the clinical research of antifungal drugs.
timeFrame: Prospective
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: St. Mary's Hospital
Study officials:
affiliation: St. Mary's Hospital, The Catholic Univ. of Korea
name: Dong-Gun Lee, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim SH, Yim DS, Choi SM, Kwon JC, Han S, Lee DG, Park C, Kwon EY, Park SH, Choi JH, Yoo JH. Voriconazole-related severe adverse events: clinical application of therapeutic drug monitoring in Korean patients. Int J Infect Dis. 2011 Nov;15(11):e753-8. doi: 10.1016/j.ijid.2011.06.004. Epub 2011 Aug 9.