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 μg/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 μg·ml(−1)/kg·day(−1)), and 7.68 (IQR, 4.07–16.3 μg·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 μg·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.