demethylmirtazapine and Depressive-Disorder

This study evaluated the effects of the CYP2D6*10 genotype on steady-state plasma concentrations of enantiomeric mirtazapine (MIR) and N-desmethylmirtazapine (DMIR) in Japanese patients.. Subjects were 77 Japanese patients treated with racemic MIR. Steady-state plasma concentrations of MIR and DMIR enantiomers were measured using stereoselective liquid chromatography. Polymerase chain reaction was used to determine the CYP2D6 genotypes.. After correcting for dose and body weight, smokers (n=15) had significantly lower S-(+)-MIR than nonsmokers (n=55) (15.1±17.8 vs. 23.9±17.8 ng/mL/mg/kg, Kruskal-Wallis test, p=0.034). One-way analysis of variance revealed that CYP2D6*10 homozygotes had significantly higher corrected plasma concentrations of S-(+)-MIR than the no-variant allele group (p=0.034). Multiple regression analysis revealed a significant positive correlation between the number of CYP2D6*10 alleles and corrected plasma concentrations of S-(+)-MIR. These results yielded the following final model: corrected plasma concentration of S-(+)-MIR=15.9+7.30×(number of CYP2D6*10 alleles) (R=0.279, p=0.023, coefficient of determination (R(2))=0.078).. Homozygous CYP2D6*10 alleles and smoking have a significant impact on the metabolism of S-(+)-MIR in Japanese patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Antidepressive Agents, Tricyclic; Cytochrome P-450 CYP2D6; Depressive Disorder; Female; Genotype; Humans; Japan; Male; Mianserin; Middle Aged; Mirtazapine; Pharmacogenetics; Young Adult

Topics: Adult; Antidepressive Agents, Tricyclic; Biotransformation; Depressive Disorder; Dialysis Solutions; Female; Humans; Mianserin; Mirtazapine; Renal Dialysis; Renal Insufficiency

Little information exists on the concentrations of recent antidepressants and their metabolites in cerebrospinal fluid (CSF). Using a stereoselective method, we measured plasma and CSF levels of mirtazapine (MIR), N-demethylmirtazapine and 8-OH-MIR in 3 depressed patients treated with racemic MIR (45 mg/day) for 4 weeks. S-(+)-MIR is considered to be the antidepressant enantiomer, but only R-(-)-MIR reached measurable concentrations in CSF. For R-(-)-MIR, the CSF/plasma ratio varied between 0.08 and 0.31. Further studies are needed to test the hypothesis that there are possible differences in the transport mechanisms of the enantiomers of MIR at the blood-CSF barrier.

Topics: Adult; Antidepressive Agents, Tricyclic; Depressive Disorder; Drug Administration Schedule; Humans; Male; Mianserin; Mirtazapine; Severity of Illness Index; Stereoisomerism