title: The impact of CYP2D6 genotypes on the plasma concentration of paroxetine in Japanese psychiatric patients.
abstract: The authors investigated the impact of the CYP2D6 genotypes on the plasma concentration of paroxetine (PAX) in 55 Japanese psychiatric patients. They were administered 10 to 40 mg/day (24+/-10.0 mg/day) of PAX and maintained at the same daily dose for at least two weeks to obtain the steady-state concentrations. The plasma levels of PAX were 15.8+/-15.0, 47.4+/-32.0, 101.2+/-59.9 and 177.5+/-123.6 ng/ml at the daily dose of 10, 20, 30 and 40 mg, respectively, which suggested dose dependent kinetics of PAX. The allele frequencies of the CYP2D65, CYP2D610 and CYP2D641 were 1.8%, 41.8% and 1.8%, respectively. Significantly higher PAX concentrations were observed in the patients having one functional allele compared with those with two functional alleles (150.9+/-20.6 vs. 243.6+/-25.2 ng/ml mg(-1) kg(-1), p<0.05, Newman-Keuls multiple comparison test) or no functional (243.6+/-25.2 vs. 76.7+/-6.1 ng/ml mg(-1) kg(-1), p<0.05, Newman-Keuls multiple comparison test) in the subjects with 30 mg/day of paroxetine. The same trend of findings as in the subjects treated with 30 mg/day were observed in the subjects with 40 mg/day of PAX. The present results suggest that having one non-functional allele is the marker for high plasma concentration of PAX when relatively high daily dose of PAX is administered.
authors.affiliation: Department of Psychiatry, Shiga University of Medical Science, Seta Tsukinowacho, Otsu, Shiga, 520-2192, Japan.
authors.forename: Mikito
authors.initials: M
authors.lastname: Ueda
authors.forename: Genta
authors.initials: G
authors.lastname: Hirokane
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Morita
authors.forename: Masako
authors.initials: M
authors.lastname: Okawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Akiyama
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Shimoda
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007564:Japan / Q000208:ethnology; D008297:Male; D001523:Mental Disorders / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D008875:Middle Aged; D017374:Paroxetine / Q000097:blood* / Q000627:therapeutic use; D012044:Regression Analysis; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood* / Q000627:therapeutic use
chemical_list: D019389:Cytochrome P-450 CYP2D6; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors