Effect of CYP2C19 polymorphism on the plasma voriconazole concentration and voriconazole‐to‐voriconazole‐N‐oxide concentration ratio in elderly patients

Background Effects of CYP2C19 polymorphism on voriconazole concentration (C 0 ), dose‐adjusted trough concentrations (C 0 /dose) and voriconazole‐to‐voriconazole‐N‐oxide concentration ratio (C 0 /C N ) have not been fully investigated. Objectives To investigate correlations of CYP2C19 polymorphisms with plasma concentrations of voriconazole and the major metabolite voriconazole‐N‐oxide in elderly patients. Methods A prospective, multi‐centre, non‐intervention, open clinical study was conducted within Southwestern Chinese patients clinically diagnosed with invasive fungal infections, to investigate the associations of CYP2C19∗2 (681G > A), CYP2C19∗3 (636G > A) and CYP2C19∗17 (−806C > T) genetic polymorphisms with voriconazole C 0 , C 0 /dose and C 0 /C N . Results The study included 131 adult patients, of which 72 were elderly (≥60 years) and 59 were adults (<60 years). The allele frequencies of CYP2C19∗2 , ∗3 and ∗17 in the elderly cohort were 61.1%, 29.9% and 7.6%, respectively, which were similar to those in the adult cohort (66.9%, 29.7% and 2.5%, respectively; P  > .05). The median voriconazole C 0 (C 0 ), C 0 /dose and C 0 /C N ratio in patients with the CYP2C19∗1/∗2 and CYP2C19∗2/∗2 genotypes were significantly higher than those in patients with the CYP2C19∗1/∗1 genotype in the adult cohort ( P <  .05). The C 0 and C 0 /dose in patients with the CYP2C19∗1/∗3 and CYP2C19∗2/∗2 genotypes, and the C 0 /C N ratio for patients with the CYP2C19∗1/∗2 genotype were numerically higher than those in patients with the CYP2C19∗1/∗1 genotype in the elderly cohort, but this difference was not statistically significant ( P >  0.05). The C 0 , C 0 /dose and C 0 /C N in patients with poor metaboliser phenotypes were higher than in those with normal metaboliser phenotypes and C 0 in patients with intermediate metaboliser phenotypes were significantly higher than in those with normal metaboliser phenotypes in the adult cohort ( P  < .05). However, there were no significant differences in the C 0 , C 0 /dose and C 0 /C N among different CYP2C19‐predicted metabolic phenotypes in the elderly cohort. Conclusions Voriconazole C 0 , C 0 /dose and C 0 /C N ratio are not significantly affected by the CYP2C19∗2 / ∗3 polymorphisms in the elderly patients.