Impact of CYP2D6*10 polymorphism on the pharmacokinetics of mirtazapine and its desmethylated metabolite in Japanese psychiatric patients treated with mirtazapine

Purpose: This study evaluated the impact of CYP2D6 polymorphism, and particularly CYP2D6*10 alleles, on the steady-state plasma concentrations of mirtazapine (MIR) and its metabolite N-desmethylmirtazapine (DMIR) in Japanese psychiatric patients.Patients and Methods: The subjects were 75 Japanese patients treated with racemic MIR. The steady-state plasma concentrations of MIR and DMIR were measured using liquid chromatography. The CYP2D6 genotypes were determined by polymerase chain reaction. Three subjects whose plasma levels of MIR and DMIR were below the limit of detection were regarded as non-adherent and excluded, and 4 subjects having the CYP2D6*5 allele (CYP2D6*1/CYP2D6*5 and CYP2D6*2/CYP2D6*5 (n = 3) and CYP2D6*5/CYP2D6*10 (n = 1)) were excluded from the analysis in order to eliminate the effect of the CYP2D6*5 allele. Accordingly, data from 68 subjects were subjected to analysis.Results: There were no significant differences in the plasma concentrations of MIR or DMIR (all corrected for dose and body weight) among different CYP2D6 genotypes. Multiple regression analysis also revealed that age affects MIR (corrected for dose and body weight) (p=0.079). Also, multiple regression analysis revealed that age correlated significantly to the plasma concentration of DMIR (corrected for dose and body weight) (p=0.026). Neither sex nor the number of CYP2D6*10 alleles were significant factors for either the plasma concentration of MIR (corrected for dose and body weight) or the plasma concentration of DMIR (corrected for dose and body weight).Conclusion: CYP2D6*10 polymorphism did not significantly affect the steady-state plasma levels of MIR and DMIR in Japanese patients, but age had a significant effect on the plasma levels of DMIR.