| Abstract |
Voriconazole is an antifungal agent recommended as the first line treatment for invasive aspergillosis infection. Voriconazole has a narrow therapeutic range and zero order metabolism. Therefore, therapeutic drug monitoring needs to be performed to achieve a therapeutic level (1-5 ug/ml). The previous study reported CYP2C19 polymorphisms correlated with the voriconazole trough concentration. The aim of this study was to determine correlation between the voriconazole dosage regimen at therapeutic range and CYP2C19 polymorphisms in Thai invasive fungal infection patients. Moreover, prevalence of CYP2C19 allelic variants in Thai healthy volunteers was investigated comparing that to other ethnic groups. One hundred Thai healthy volunteers and 80 invasive fungal infection patients treated with voriconazole were enrolled. CYP2C19 polymorphisms were genotyped in both healthy volunteers and the patients. The prevalence of Thai CYP2C19 variants (CYP2C19*1/*1 50%, *1/*2 36%, *1/*3 6%, *2/*2 6%, *2/*3 1% and *1/*17 1%, respectively) was similar to Korean and Chinese populations, but it was different from Japanese, Caucasian, Ugandan and Russian populations. Moreover, correlation between the voriconazole dosage regimen and the CYP2C19 genotypes was determined. The patients with poor metabolizers tended to require lower dose of voriconazole than patients with extensive and intermediate metabolizers (7.31±0.72 VS 8.38±0.31 mg/day, respectively, P=0.298). Nevertheless, no statistically significant difference of the correlation between CYP2C19 mutations and voriconazole doses was found in this study.
Keywords: CYP2C19 polymorphisms, Voriconazole, Dosage regimen, Invasive fungal infection |
Publication
Journal Publication
ไทย