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

• Published in: Mycoses Vol. 63; no. 11; pp. 1181 - 1190
• Main Authors: Shang, Shenglan, Cheng, Lin, Li, Xiaoyu, Xiang, Rongfeng, Yu, Mingjie, Xiong, Lirong, Chen, Yongchuan
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-11-2020
• Subjects: CYP2C19; elderly; Gene frequency; Gene polymorphism; Genotype & phenotype; invasive fungal infections; Metabolites; Phenotypes; plasma concentration; Polymorphism; Statistical analysis; therapeutic drug monitoring; Voriconazole; voriconazole‐N‐oxide; Voriconazole; Voriconazole N-oxide; CYP2C19; plasma concentration; Elderly; Gene polymorphism; Invasive fungal infections; therapeutic drug monitoring
• ISSN: 0933-7407; 1439-0507
• DOI: 10.1111/myc.13105

Background
Effects of CYP2C19 polymorphism on voriconazole concentration (C0), dose‐adjusted trough concentrations (C0/dose) and voriconazole‐to‐voriconazole‐N‐oxide concentration ratio (C0/CN) 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 C0, C0/dose and C0/CN.
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 C0 (C0), C0/dose and C0/CN 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 C0 and C0/dose in patients with the CYP2C19∗1/∗3 and CYP2C19∗2/∗2 genotypes, and the C0/CN 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 C0, C0/dose and C0/CN in patients with poor metaboliser phenotypes were higher than in those with normal metaboliser phenotypes and C0 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 C0, C0/dose and C0/CN among different CYP2C19‐predicted metabolic phenotypes in the elderly cohort.
Conclusions
Voriconazole C0, C0/dose and C0/CN ratio are not significantly affected by the CYP2C19∗2/∗3 polymorphisms in the elderly patients.