title: Factors Affecting Steady-state Plasma Concentrations of Enantiomeric Mirtazapine and its Desmethylated Metabolites in Japanese Psychiatric Patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Homozygous CYP2D6*10 alleles and smoking have a significant impact on the metabolism of S-(+)-MIR in Japanese patients.
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Aoki
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ishiguro
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Akiyama
authors.affiliation: Sakura La Mental Clinic, Youtou, Utsunomiya, Tochigi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Neuropsychiatry, Hirosaki University Graduate School of Medicine, Zaifucho, Hirosaki, Aomori, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tsuchimine
authors.affiliation: Department of Neuropsychiatry, Hirosaki University Graduate School of Medicine, Zaifucho, Hirosaki, Aomori, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yasui-Furukori
authors.affiliation: Department of Psychiatry, Dokkyo Medical University School of Medicine, Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shimoda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000929:Antidepressive Agents, Tricyclic / Q000097:blood* / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D010597:Pharmacogenetics; D055815:Young Adult
chemical_list: D000929:Antidepressive Agents, Tricyclic; C517416:desmethylmirtazapine; D008803:Mianserin; D000078785:Mirtazapine; D019389:Cytochrome P-450 CYP2D6