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

Background Effects ofCYP2C19polymorphism 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 ofCYP2C19polymorphisms 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 ofCYP2C19*2(681G > A),CYP2C19*3(636G > A) andCYP2C19*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 ofCYP2C19*2,*3and*17in 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 theCYP2C19*1/*2andCYP2C19*2/*2genotypes were significantly higher than those in patients with theCYP2C19*1/*1genotype in the adult cohort (P .05). The C(0)and C-0/dose in patients with theCYP2C19*1/*3andCYP2C19*2/*2genotypes, and the C-0/C(N)ratio for patients with theCYP2C19*1/*2genotype were numerically higher than those in patients with theCYP2C19*1/*1genotype 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 theCYP2C19*2/*3polymorphisms in the elderly patients.