Correlation of CYP2C19 genotype with plasma voriconazole exposure in South-western Chinese Han patients with invasive fungal infections.

The aim of this study was to investigate the correlation between CYP2C19 genotype and dose-adjusted voriconazole (VCZ) trough concentrations (C-0/dose). We analyzed the correlation between CYP2C19*2(681G>A), CYP2C19*3(636G>A), and CYP2C19*17(-806C>T) genetic polymorphisms and the dose-corrected pre-dose concentration (C-0/dose) in 106 South-western Chinese Han patients. The frequencies of variant alleles of CYP2C19*2, *3, and *17 were 29.7%, 4.25%, and 0.92%. For 49.3% of the VCZ samples, the therapeutic window between 1.5 and 5.5 mu g/ml was reached. Following the first dose VCZ measurement, in subsequent samples the proportion of VCZ C-0 within the therapeutic window increased, suggesting effective therapeutic drug monitoring (TDM) (P = .001). The VCZ C-0 was significantly different (P = .010) between patients with normal metabolism (NMs), intermediate metabolism (IMs), and poor metabolism (PMs). The VZC C-0/dose was 12.2 (interquartile range (IQR), 8.33-18.2 mu g.ml(-1)/kg.day(-1)), and 7.68 (IQR, 4.07-16.3 mu g.ml(-1)/kg.day(-1)) in PMs and IMs patients, respectively, which was significantly higher than in NMs phenotype patients (4.68; IQR, 2.51-8.87 mu g.ml(-1)/kg.day(-1), P = .008 and P = .014). This study demonstrated that the VCZ C-0/dose was significantly influenced by the CYP2C19 genotype in South-western Chinese Han patients. In this patient population, more over-exposure was observed in patients with a CYP2C19 genotype associated with poor or intermediate metabolism. CYP2C19 genotype-based dosing combined with TDM will support individualization of VCZ dosing, and potentially will minimize toxicity and maximize therapeutic efficacy.