Effect of CYP2C19 Polymorphisms on Plasma Voriconazole Concentration in Patients with Immunodeficiency Disease

The purpose of this study was to describe CYP2C19 polymorphisms in a Chinese population and to evaluate voriconazole pharmacokinetics in immune deficiency patients. Overall, 215 samples were obtained from 91 patients who received voriconazole treatment from November 2018 to April 2020. Baseline patient demographics, concurrent medications, voriconazole levels, and invasive fungal disease history were collected. The relationships among therapeutic drug monitoring (TDM) data and CYP2C19 polymorphisms were assessed. The wild-type allele, CYP2C19*1, was found to be most frequent (115/182, 63%), followed by CYP2C19*2 (49/182, 26.9%), and CYP2C19*3 (16/182, 8.8%). The least frequent genotype was CYP2C19*17 (2/182, 1.1%). Approximately 60% of patients reached a therapeutic drug level between 1 and 5.5 mu g/mL. These results demonstrated voriconazole blood concentration in poor metabolizers (PM) and intermediate metabolizers (IM) to be nearly twice as high as that of extensive metabolizers (EM) and ultra-rapid metabolizers (UM), which were similar to EM or lower. Our results demonstrate the utility of CYP2C19 genotyping for the prediction of voriconazole trough plasma concentration, associated toxicity, and therapeutic effect within different Chinese phenotypes. CYP2C19 IM and PM had elevated voriconazole plasma concentrations relative to those of EM. As such, the blood concentration of voriconazole determines the therapeutic effect of the drug as well as any associated drug toxicity.