Neuropsychopharmacology reports
Distinct Associations of Age and CYP2D6 Genotype With Parent Venlafaxine Exposure and O-Demethylation in Japanese Psychiatric Patients
By Ishihara Y, Sasaki T, Asahi T and 6 others.
Abstract
Background
Venlafaxine (VEN) is converted to O-desmethylvenlafaxine (ODV) mainly through CYP2D6-mediated O-demethylation. However, age-related clinical factors may also influence VEN exposure in routine practice. We examined whether age and CYP2D6 genotype show different associations with parent-drug exposure and metabolic conversion.
Methods
This retrospective therapeutic drug monitoring analysis included 78 Japanese psychiatric patients with available plasma VEN and ODV concentrations and CYP2D6 genotype data. Two prespecified outcomes were analyzed without body-weight correction: VEN concentration divided by daily dose (VEN/dose) and the ODV/VEN ratio. CYP2D6*10 and *5 were coded as reduced- and no-function alleles, respectively. Log-transformed outcomes were analyzed using regression models including age and CYP2D6 reduced/no-function allele count.