Interaction of age and CYP2C19 genotypes on voriconazole steady-state trough concentration in Chinese patients

Abstract

Objectives Both age and CYP2C19 genotypes affect voriconazole plasma concentration; the interaction of age and CYP2C19 genotypes on voriconazole plasma concentration remains unknown. This study aims to investigate the combined effects of age and CYP2C19 genotypes on voriconazole plasma concentration in Chinese patients. Methods A total of 480 patients who received voriconazole treatment were recruited. CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) polymorphisms were genotyped. Patients were divided into the young and the elderly groups by age of 60 years old. Influence of CYP2C19 genotype on steady-state trough concentration (Css-min) in overall patients and in age subgroups was analyzed. Results Voriconazole Css-min correlated positively with age, and mean voriconazole Css-min was significantly higher in the elderly group (P < 0.001). CYP2C19 poor metabolizers showed significantly increased mean voriconazole Css-min in the young but not the elderly group. The percentage of patients with subtherapeutic voriconazole Css-min (<1.0 mg/l) was higher in the young group and that of supratherapeutic voriconazole Css-min (>5.5 mg/l) was higher in the elderly patients. When the average Css-min in the CYP2C19 normal metabolizer genotype was regarded as a reference, CYP2C19 genotypes showed greater impact on voriconazole Css-min in the young group, while the influence of age on voriconazole Css-min exceeded CYP2C19 genotypes in the elderly. Conclusion CYP2C19 genotypes affects voriconazole exposure is age dependent. Influence of CYP2C19 poor metabolizer genotype on increased voriconazoleexposure is prominent in the young, while age is a more important determinant factor for increased voriconazole exposure in the elderly patients.