Effect of cyclosporine a and polymorphisms in <i>CYP2C19</i> and <i>ABCC2</i> on the concentration of voriconazole in patients undergoing allogeneic hematopoietic stem cell transplantation

Abstract

1. Voriconazole is known to display highly variable pharmacokinetics affecting treatment efficacy and safety. This study aimed to identify the factors causing the variation of voriconazole concentration in patients with allogeneic hematopoietic stem cell transplantation.2. The data of patients was collected, including clinical characteristics and voriconazole concentrations. A total of 5 single nucleotide polymorphisms of 3 candidate genes (<i>CYP2C19, ABCC2, ABCG2</i>) related to voriconazole metabolism were genotyped by MassArray method. The correlation between polymorphisms and voriconazole concentration was analyzed.3. A total of 244 voriconazole concentrations of 43 patients were included in this study. The voriconazole concentration was significantly correlated with patients' total bile acid (<i>p</i> = 0.001) and cyclosporin A (<i>p</i> < 0.001). The median concentration of the <i>CYP2C19</i> normal metabolizers was remarkably lower than poor metabolizers (0.86 vs 2.27 μg/mL). The median concentration of <i>ABCC2 rs2273697</i> GG genotype carriers was significantly higher than that of GA genotype carriers (<i>p</i> = 0.026).4. The variability of voriconazole concentration is partially explained by total bile acid, metabolic types of <i>CYP2C19</i>. The voriconazole concentration of <i>CYP2C19</i> normal metabolizers is likely to be lower than 1.0 μg/mL and thus at risk of infection due to inadequate treatment.