Serum concentrations of risperidone and aripiprazole in subgroups encoding CYP2D6 intermediate metabolizer phenotype

Area of Science:

• Pharmacogenomics
• Clinical Chemistry
• Psychiatric Pharmacology

Background:

• Cytochrome P450 2D6 intermediate metabolizer (CYP2D6 IM) phenotype encompasses diverse genotype subgroups.
• Understanding these variations is crucial for optimizing drug therapy.

Purpose of the Study:

• To evaluate serum concentrations of risperidone and aripiprazole.
• To assess these concentrations in psychiatric patients with various CYP2D6 genotypes linked to the IM phenotype.

Main Methods:

• Analysis of therapeutic drug monitoring data from CYP2D6-genotyped patients (n=190 risperidone, n=266 aripiprazole).
• Categorization into three CYP2D6 IM genotype subgroups: *1/def, red/red, and def/red.
• Comparison of dose-adjusted serum concentrations against the *1/def reference group.

Main Results:

• Median serum concentrations were 4.5-fold higher for risperidone and 1.6-fold higher for aripiprazole in the def/red genotype compared to *1/def.
• Serum concentrations were 3.4-fold higher for risperidone and 1.8-fold higher for aripiprazole in the red/red subgroup versus the reference group.

Conclusions:

• Significant variability in risperidone and aripiprazole serum concentrations exists among CYP2D6 IM genotypes.
• A notable phenotypic difference was observed between patients with one versus two variant alleles, impacting drug levels.