The impact of CYP2D6 genotypes on the plasma concentration of paroxetine in Japanese psychiatric patients.
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.
Ueda
Mikito
M
Department of Psychiatry, Shiga University of Medical Science, Seta Tsukinowacho, Otsu, Shiga, 520-2192, Japan.
Hirokane
Genta
G
Morita
Sachiyo
S
Okawa
Masako
M
Watanabe
Takashi
T
Akiyama
Kazufumi
K
Shimoda
Kazutaka
K
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
D019389:Cytochrome P-450 CYP2D6; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors