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 ), dose-adjusted trough concentrations (C /dose) and voriconazole-to-voriconazole-N-oxide concentration ratio (C /C ) 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 , C /dose and C /C .

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 (C ), C /dose and C /C 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 and C /dose in patients with the CYP2C19∗1/∗3 and CYP2C19∗2/∗2 genotypes, and the C /C 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 , C /dose and C /C in patients with poor metaboliser phenotypes were higher than in those with normal metaboliser phenotypes and C 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 , C /dose and C /C among different CYP2C19-predicted metabolic phenotypes in the elderly cohort.

Conclusions: Voriconazole C , C /dose and C /C ratio are not significantly affected by the CYP2C19∗2/∗3 polymorphisms in the elderly patients.