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The impact of CYP2D6 genotypes on the plasma concentration of paroxetine in Japanese psychiatric patients

, : The impact of CYP2D6 genotypes on the plasma concentration of paroxetine in Japanese psychiatric patients. Progress in Neuro-Psychopharmacology & Biological Psychiatry 30(3): 486-491

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 CYP2D6*5, CYP2D6*10 and CYP2D6*41 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, NewmanKeuls multiple comparison test) or no functional (243.6 +/- 25.2 vs. 76.7 +/- 6.1 ng/mI 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. (c) 2005 Elsevier Inc. All rights reserved.


PMID: 16423440

DOI: 10.1016/j.pnpbp.2005.11.007

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